Brain cells and aging

Within the majority of the brain the type of brain cells that send nerve signals generally do not get replaced, however they also generally don’t lose function. Dementia – loss of memory and other cognitive skills – is not a normal part of healthy aging. Age related forgetfulness has to do with loss of the connections between brain cells but the brain cells remain functional – so continuing to take part in learning and social activities may help prevent dementia and forgetfulness by helping to maintain current connections between brain cells and add new connections formed during learning or socializing. 

And yet Alzheimer’s dementia now “afflicts 5% to 10% of the U.S. population over the age of 65 and as much as 45% of the population over 85.” (page 694, Neuroscience, 6th. edition, 1)

Research for medications for Alzheimer’s treatment have focused on reducing the levels of certain types of protein that collect in the damaged areas of the brain of a patient with the condition, however even if successful at reducing the amount of the protein the medications have not been found very helpful for restoring the patient’s cognitive health. (previous post) People with normal brain function also can have excess of the protein and it is also found in the brains of people with autism disorder – confusing, yes. Adequate quality sleep may help the brain waste removal system keep the levels of excess protein from building up to damaging amounts. (previous post on sleep and the glymphatic system)

Things that may increase risk include chronic stress and the excess cortisol and inflammatory oxidative stress chemicals production. Moderate exercise may help reduce stress and promote detoxification of inflammatory chemicals. Staying socially and mentally active also may be protective of brain function. Prevention is the best medicine for conditions that cause irreversible degenerative changes such as the damage in Alzheimer’s Disease. Learning about new foods and recipes and then making healthy meals to share with others can be a way to combine physical and mental activity and gain from nutrients that help detoxify inflammatory oxidative stress chemicals. (previous post, Foods for beneficial T-cells) – (Nrf2 promoting foods)

T cells are a type of blood cell with immune system functions. Beneficial T cells can help clear excess protein found in Alzheimer’s (2) while other types can increase inflammation and the types can transform based on the level of oxidative stress chemicals that are present so having antioxidants and other phytonutrients in daily meals can help signal the T-cells to take the beneficial forms instead of the inflammatory forms. (The non euphoria producing endogenous cannabinoid 2-AG (acts at the CB2 receptor, somewhat similar to CBD) may also help signal T cells towards the less inflammatory type, and reduce migration of them. page 96)

Nrf2 is a gene and protein that help promote the more beneficial types of T cells and help the immune system in other ways and also promote our own production of antioxidants for reducing the oxidative stress chemicals that are a natural waste product left from energy metabolism – when blood sugar is turned into a usable form of energy.

The long story is complicated, the short story remains,

  • include moderate exercise most days of the week,
  • have adequate sleep, 6-8 hours/night, ideally with complete darkness, blackout curtains and cover the light from an electric bedside alarm clock (put it in a nearby drawer or cover it with something),
  • get some natural sunshine or full spectrum light during the day if possible (may help with vitamin D, bioactive sulfate, and circadian rhythm metabolism within the body which includes production of melatonin,
  • stay mentally and socially active,
  • reduce stress when possible and/or practice relaxation techniques,
  • drink adequate water and regularly eat a good variety of colorful fresh produce, whole grains, nuts, beans, seeds, and include omega 3 fatty acid sources on a daily or weekly basis.
  • Clean air quality is also important. Formaldehyde (from secondhand smoke or even excessive use of decorative candles), and other air pollutants (released by plastics or new carpeting/flooring for example) can collect in poorly ventilated buildings. See this post for more information about formaldehyde sources and ways to reduce it: Formaldehyde: Health Risks, and Environmental and Dietary Sources.(effectiveselfcare.info)
  • Adequate water, not getting dehydrated regularly, is important enough to repeat because dehydration allows toxins within the body, including formaldehyde, to collect, instead of being removed by the glymphatic/lymphatic and vascular system, and to then be excreted by the kidneys. Brain Formaldehyde is Related to Water Intake Behavior, Ting Li, et al, 2016, (PubMed) A discussion of how much water is typically needed for health each day, and how much protein to eat for basic needs without being too much for long term kidney health, is available in a previous post: Make Every Day Kidney Appreciation Day. (effectiveselfcare.info)

More of the long story – the Cannabinoid Receptor Type 2 is also activated by a phytonutrient called beta-caryophyllene (BCP) which is found in many aromatic herbs and spices including: oregano, cinnamon,  clove , rosemary,  thyme, black pepper, (4), and copaiba oil. (5) Benefits may include reducing inflammation and pain, anti-anxiety, anti-cancer, (4), and protection of the brain by helping reduce increased activity after brain trauma which can lead to scar like tissue walling off the area of trauma instead healing.(5)

The problem in Alzheimer’s may not be the protein itself but instead the cells that over-actively making it in response to inflammatory signals so the solution would be not trying to remove excess protein but to stop the production of excess protein by signaling the overactive cells that all is well again, stop walling off the supposed injury. Formalin, a more dilute buffered form of formaldehyde was the toxin used to create inflammation in an animal based study of the potential benefits of beta-caryophyllene. A dose of 5 mg/Kg purified beta-caryophyllene essential oil given by mouth (rather than by an injection) was found to help reduce inflammatory pain from the formalin. (4) For a 75 kilogram adult that would be a capsule with 375 milligrams of the purified oil.

The herb rosemary is pine needle like plant that has been used as a pain killer in traditional folk medicine for arthritis pain and was thought of a s a memory aid. Studies more recently have found the essential oil beneficial for improving memory. (6)  **Use care when purchasing essential oils, some are intended only for external use either on the skin when diluted in a small amount of milder oil such as almond oil for massage or topical pain relief, or as an aromatic for scent (example, put a few drops on a cotton ball that is attached to a fan or on the outlet of a humidifier to circulate the aroma through a room).

/Disclosure: This information is provided for educational purposes within the guidelines of fair use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes./

  1.  Neuroscience, 6th Edition, Editors D. Purves, G.J. Augustine, D. Fitzpatrick, W.C. Hall, A.S. LaMantia, R.D. Mooney, ML. Platt, L.E. White, (Sinauer Associates, Oxford University Press, 2018, New York) (Barnes&Noble)
  2. Anna Mietelska-Porowska and Urszula Wojda, “T Lymphocytes and Inflammatory Mediators in the Interplay between Brain and Blood in Alzheimer’s Disease: Potential Pools of New Biomarkers,” Journal of Immunology Research, vol. 2017, Article ID 4626540, 17 pages, 2017. https://doi.org/10.1155/2017/4626540. https://www.hindawi.com/journals/jir/2017/4626540/
  3. edited by Karsten Sauer, Klaus Okkenhaug, Lipid Signaling in T Cell Development and Function, Frontiers Media SA, Nov 12, 2015 page 96
  4. A.-L.Klauke, I.Racz, B.Pradier, et al., The cannabinoid CB2 receptor-selective phytocannabinoid beta-caryophyllene exerts analgesic effects in mouse models of inflammatory and neuropathic pain. European Neuropsychopharmacology, Vol. 24, Issue 4, April 2014, Pages 608-620, https://www.sciencedirect.com/science/article/pii/S0924977X13003027
  5. Guimarães-Santos A, Santos DS, Santos IR, et al. Copaiba Oil-Resin Treatment Is Neuroprotective and Reduces Neutrophil Recruitment and Microglia Activation after Motor Cortex Excitotoxic Injury. Evidence-based Complementary and Alternative Medicine : eCAM. 2012;2012:918174. doi:10.1155/2012/918174. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3291111/
  6. Rachel Hosie, Surge in Rosemary Sales as Aromatic Herb Found to Boost Memory, May 19, 2017, independent.co.uk,  https://www.independent.co.uk/life-style/health-and-families/rosemary-sales-surge-herb-boost-memory-holland-barrett-a7745231.html

Glymphatic system – yes- sleep helps protect against Alzheimer’s dementia

Following up on Friday’s easy answer day (previous post) – yes, the glymphatic system of the brain does help protect against Alzheimer’s dementia, (7, 8, 14, 17), and sleep, especially one of the deeper stages of sleep (low-delta), is important. (10, 11, 13) Sleeping on your right side may help promote better fluid drainage through the glymphatic system of the brain (sleeping on your right side puts the left side of your body with your heart farther up above the rest of your body, a pillow between your knees and a neck support may also help). (Social media link, reference source: Neurology Reviews, 2) (12) *I had trouble finding anything very specific about whether right or left side was better for glymphatic and lymphatic drainage – this article from an Ayurveda specialist describes how the anatomy is better suited to sleeping on the left side than the right side – the aorta leaves the heart on the left so laying on the left side allows the flow to go downhill with the aid of gravity. (https://lifespa.com/amazing-benefits-of-sleeping-on-your-left-side/ )

The circulation by the heart can help move fluid through the brain but only indirectly due to the on/off pressure of the arterial pulse. The regular lymphatic system of the body is a drainage system for the brain fluid system but the blood brain barrier prevents direct interaction. Specialized water pumps in some types of brain glial cells help provide circulation within the brain by pumping water in two directions within the second layer of thick membranes that separate the soft brain tissue from the bony skull. (3)(4)(15)(16)

Overall the fluid within the brain does circulate and there is a visible, small, pulsing movement that has been amplified and can be observed in a video: (5). The spread of a dye within the brain can be observed in a different type of brain scan, the fluid diffusion is not rapid taking 24 hours to reach a maximal point, and the movement of the dye was most prevalent (see color chart) near the skull: (6). The glymphatic system as defined as the specialized glial cells with water pump channels is located in the area near the skull. (4) Diffusion of fluid throughout deeper areas of the brain where the blood brain barrier is not found can occur to a small extent through membranes. (9)

Exercise may also help the glymphatic system function better. (18) The lymphatic vessels and lymph nodes in the neck are the initial drainage route for the glymphatic system cleansing of the various fluid filled areas of the brain. Stretching exercises and rhythmic walking type exercise can help move lymphatic fluid from farther areas of the body to the torso and urinary system for eventual excretion.

Small amounts of alcohol – one third of a serving; to moderate – one or two servings per day (too much may not be helpful); may help the detoxification of the brain fluid by mechanisms that are not well understood yet but which seem to involve the glymphatic system. (19, 20) The mechanism may involve the effect of alcohol on GABA receptors, it can activate them which in general would have a calming/inhibitory effect, (23), however GABA receptors also are involved in promoting more production of the water pump Aqaporin 4 channels in neural stem cells within the subependymal zone. (24) The subependymal zone is in the lateral part of the lateral ventricle which is a cerebrospinal fluid filled area near the center of the brain, (27), which is involved in fluid balance and drainage of the glymphatic system. (25) GABA receptors are also involved with flow of chloride ions across membranes (for an inhibitory effect on nerve signaling, (pp 126-131, 1), and affect fluid balance in areas of the brain without the blood brain barrier which makes diffusion of water across the brain membranes more possible. (26)

Alcohol also inhibits the action of the excitatory neurotransmitter glutamate, particularly at the NMDA receptor, (23), which is an excitatory ion channel and also allows calcium to enter the cell where the mineral can activate many functions within the cell. (pp 120-126, 1) If drinking alcohol is not preferred or legal due to age or advised due to pregnancy or possibility of becoming pregnant then GABA (gamma-aminobutyric acid) is available as an over the counter supplement, typically in a form that melts in the mouth to promote more direct absorption. While it is not typically referred to as an amino acid due to its role as a neurotransmitter, it is simply an amino acid, a smaller molecule from which proteins can be formed. The level of GABA a has been found to be reduced in the brains of patients with severe Alzheimer’s Disease and its use as a treatment has been studied, (29), levels in other abnormal brain cells were found to be elevated in a specific area of the brain of patients with Alzheimer’s Disease and treatment to increase transport of GABA has also been studied. (30)

Or sleep, in the form of a short nap, may also help promote GABA. Naps may benefit our health in part because of a beneficial effect on GABA promotion by increased glymphatic action in the brain – twenty minutes of sleep may be adequate. (28)

An overview of the glymphatic system and lifestyle and dietary tactics that might improve its function are described in a video by a nutritionist: (21); and also in a self-help style article by a different person: (22).

Some types of magnesium supplements including magnesium threonate may also help. Magnesium within the brain has many functions including inhibiting the NMDA glutamate receptor which would prevent excess calcium from entering the cell. (pp 120-126, 1)

We tend to hear about neurotransmitters such as serotonin for depression or dopamine and Parkinson’s disease, yet we rarely hear that calcium is the mineral that signals the release of both of those and over one hundred other neurotransmitters that are involved in nerve signals within the brain or throughout the body (page 85, 1.Neuroscience, 6th Ed.). Neurotransmitters include excitatory and inhibitory chemicals and they activate or inhibit the firing of a nerve signal. GABA can be a calming/inhibitory neurotransmitter that may be low when anxiety is a problem. Magnesium is the mineral inside cells which helps control how much calcium will be allowed to enter. Excess calcium can cause excess release of neurotransmitters. Magnesium deficiency can also be involved when anxiety is a symptom.

Adequate fluid is also likely important for adequate cleansing of waste from the brain by the glymphatic system. Problems with edema/swelling in other areas of the body or problems with hypertension may indicate problems with the lymphatic system in general. Moderate exercise helps the muscle power of movement also move extracellular fluid and lymphatic fluid through the lymphatic vessels to lymph nodes to be filtered by blood cells. Waste is removed into blood vessels for later excretion by the kidneys.

Additional note – adenosine was mentioned in the series on demyelination as a chemical that may lead to more breakdown of cells or myelin. It is produced as a metabolite of normal energy production and increased levels seem to be involved in our beginning to feel sleepy, signaling a need for rest – which would then give the brain clean up glymphatic system a chance to work on decreasing levels — so feeling sleepy? Your brain may be trying to tell you it is time to clean up after a strenuous workout whether physical or mental.  (See the What Makes You Sleep? section in the NHLBI article about Sleep Deprivation and Deficiency)

For more general information about promoting sleep and coping with insomnia see the post “Sleep and Health.”

Disclaimer: Opinions are my own and the information is provided for educational purposes within the guidelines of fair use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes.

  1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4326841/Reference: pp 85-112, “Synaptic Transmission,” Neuroscience, 6th Edition, Editors D. Purves, G.J. Augustine, D. Fitzpatrick, W.C. Hall, A.S. LaMantia, R.D. Mooney, ML. Platt, L.E. White, (Sinauer Associates, Oxford University Press, 2018, New York) (Barnes&Noble)
  2. Glymphatic System May Play Key Role in Removing Brain Waste, Neurology Reviews, 2016 October;24(10):13   https://www.mdedge.com/neurologyreviews/article/114150/alzheimers-cognition/glymphatic-system-may-play-key-role-removing
  3. Understanding the Glymphatic System, Neuronline, adapted from the SfN Short Course The Glymphatic System by Nadia Aalling, MSc, Anne Sofie Finmann Munk, BSc, Iben Lundgaard, PhD, and Maiken Nedergaard, MD, DMSc http://neuronline.sfn.org/Articles/Scientific-Research/2018/Understanding-the-Glymphatic-System
  4. Tsutomu Nakada, Ingrid L. Kwee, Fluid Dynamics Inside the Brain Barrier: Current Concept of Interstitial Flow, Glymphatic Flow, and Cerebrospinal Fluid Circulation in the Brain. The Neuroscientist, May 24, 2018, http://journals.sagepub.com/doi/10.1177/1073858418775027#articleCitationDownloadContainer
  5. Bruce Goldman, The beating brain: A video captures the organ’s rhythmic pulsations. Scope, Stanford Medicine, July 5, 2018, https://scopeblog.stanford.edu/2018/07/05/the-beating-brain-a-video-captures-the-organs-rhythmic-pulsations/?linkId=53912604
  6. Geir Ringstad, Lars M. Valnes, Anders M. Dale, et al., Brain-wide glymphatic enhancement and clearance in humans assessed with MRI. JCI Insight. 2018;3(13):e121537 https://insight.jci.org/articles/view/121537?utm_content=buffer13f62&utm_medium=social&utm_source=twitter.com&utm_campaign=buffer
  7. Brain discovery could block aging’s terrible toll on the mind. University of Virginia Health System, EurekAlert! Science News, July 25, 2018, https://www.eurekalert.org/pub_releases/2018-07/uovh-bdc072518.php
  8. Da Mesquita S., Louveau A., Vaccari A., et al., Functional aspects of meningeal lymphatics in ageing and Alzheimer’s disease, Nature, 185,191, Vol 560, Issue 7717, 2018/08/01. https://www.nature.com/articles/s41586-018-0368-8
  9. Albargothy N. J., Johnston D. A., MacGregor‑Sharp M., Convective influx/glymphatic system: tracers injected into the CSF enter and leave the brain along separate periarterial basement membrane pathways. Acta Neuropathologica (2018) 136:139–152 https://link.springer.com/epdf/10.1007/s00401-018-1862-7?shared_access_token=oYhOYaeYOAlkFhECIjAc6Pe4RwlQNchNByi7wbcMAY7lrBk-VqU01OilsaKMVR9FXaHRKmFQ1tkD03g-Q04DmsYSxRC_gucPZRYlFW0xfyU2pYNfhmwcokVbMCreuzU3wBLsjKpRasKo-6HXTJLMHNXMqFbaSsQVIB34EgzIUsc%3D
  10. Tamara Bhandari, Lack of Sleep Boosts Levels of Alzheimer’s Proteins, The Source, Washington University in St. Louis, Dec. 27, 2017, https://source.wustl.edu/2017/12/lack-sleep-boosts-levels-alzheimers-proteins/
  11. Yo-El S Ju, Sharon J Ooms, Courtney Sutphen, et al., Slow wave sleep disruption increases cerebrospinal fluid amyloid-β levels. Brain, Vol 140, Issue 8, 1 August 2017, Pages 2104–2111, Oxford Academic, https://academic.oup.com/brain/article/140/8/2104/3933862
  12. Krista Burns, American Posture Institute: Proper Sleeping Posture for ‘Brain Drain,’ April 5, 2017, https://americanpostureinstitute.com/proper-sleeping-posture-for-brain-drain/
  13. Patricia Farrell, Sleep: Everyone Needs It and So Do You, March 16, 2017, https://www.amazon.com/dp/152061294X
  14. Melanie D. Sweeney, Berislav V. Zlokovic, A lymphatic waste-disposal system implicated in Alzheimer’s disease. July 25, 2018, https://www.nature.com/articles/d41586-018-05763-0?utm_source=twt_na&utm_medium=social&utm_campaign=NNPnature
  15. Nadia Aalling Jessen, Anne Sofie Finmann Munk, Iben Lundgaard, Maiken Nedergaard, The Glymphatic System – A Beginners Guide, Neurochem Res. 2015 Dec; 40(12): 2583–2599. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4636982/
  16. Maiken Nedergaard, Steven A. Goldman, Brain Drain, Sci Am. 2016 Mar; 314(3): 44–49. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5347443/
  17. Rainey-Smith S. R., Mazzucchelli G. N., Villimagne V. L., et al. Genetic Variation in Aquaporin-4 Moderates the Relationship Between Sleep and Brain Aβ-amyloid burden. Translational  Psychiatry, (2018) 8:47 https://www.nature.com/articles/s41398-018-0094-x.epdf?author_access_token=iK09AkugOzYXUjXJCpGfIdRgN0jAjWel9jnR3ZoTv0P4SU0l7P8A1C64dg2xJ-HX7jlpuvyMeHzBYm6I5D0yMRBsx023MtG5Y3KNpj4EoNEqA4ELFuByqeysfTCRKZdGegxohMN9WLBb_S6H0UZYpw%3D%3D
  18. Brown B., Rainey-Smith S. R., Dore V., et al., Self-Reported Physical Activity is Associated with Tau Burden Measured by Positron Emission Tomography. Journal of Alzheimer’s Disease, vol. 63, no. 4, pp. 1299-1305, May 30, 2018 https://content.iospress.com/articles/journal-of-alzheimers-disease/jad170998
  19. Chloe Chaplain, Drinking wine every day could help prevent Alzheimer’s, experts say. London Evening Standard, June 6, 2018, https://www.standard.co.uk/news/health/drinking-wine-every-day-could-help-prevent-alzheimers-experts-say-a3856646.html
  20. In Wine, There’s Health: Low Levels of Alcohol Good for the Brain. Feb. 2, 2018, University of Rochester Medical Center, https://www.urmc.rochester.edu/news/story/5268/in-wine-theres-health-low-levels-of-alcohol-good-for-the-brain.aspx
  21. Brianna Diorio, Glymphatic System 101, video,August 8, 2018,  https://vimeo.com/283708099?ref=tw-share
  22. Sydney, How To Detox Your Brain By Hacking Your Glymphatic System. A Healthy Body, May 18, 2018, http://www.a-healthy-body.com/how-to-detox-your-brain-by-hacking-your-glymphatic-system/
  23. The Effects of Alcohol on the Brain, The Scripps Research Institute, https://www.scripps.edu/newsandviews/e_20020225/koob2.html
  24. Li Y, Schmidt-Edelkraut U, Poetz F, et al. γ-Aminobutyric A Receptor (GABAAR) Regulates Aquaporin 4 Expression in the Subependymal Zone: RELEVANCE TO NEURAL PRECURSORS AND WATER EXCHANGE. The Journal of Biological Chemistry. 2015;290(7):4343-4355. doi:10.1074/jbc.M114.618686. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4326841/ (24)
  25. Plog BA, Nedergaard M. The glymphatic system in CNS health and disease: past, present and future. Annual review of pathology. 2018;13:379-394. doi:10.1146/annurev-pathol-051217-111018. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5803388/ (25)
  26. Cesetti Tiziana, Ciccolini Francesca, Li Yuting, GABA Not Only a Neurotransmitter: Osmotic Regulation by GABAAR Signaling. Frontiers in Cellular Neuroscience, Vol. 6, 2012, https://www.frontiersin.org/article/10.3389/fncel.2012.00003 DOI=10.3389/fncel.2012.00003 ISSN=1662-5102 (26)
  27. Kazanis I. The subependymal zone neurogenic niche: a beating heart in the centre of the brain: How plastic is adult neurogenesis? Opportunities for therapy and questions to be addressed. Brain. 2009;132(11):2909-2921. doi:10.1093/brain/awp237. (27)
  28. Robert I Henkin, Mona Abdelmeguid, Sleep, glymphatic activation and phantosmia inhibition. The FASEB Journal, Vol 31, No. 1_supplement, April 2017, https://www.fasebj.org/doi/abs/10.1096/fasebj.31.1_supplement.749.4  (28)
  29. Solas M, Puerta E, Ramirez MJ. Treatment Options in Alzheimer’s Disease: The GABA Story., Curr Pharm Des. 2015;21(34):4960-71. https://www.ncbi.nlm.nih.gov/pubmed/26365140 (29)
  30. Zheng Wu, Ziyuan Guo, Marla Gearing, Gong Chen, Tonic inhibition in dentate gyrus impairs long-term potentiation and memory in an Alzheimer’s disease model. Nature Communications, 5,  Article number: 4159 (2014) https://www.nature.com/articles/ncomms5159 (30)

Average Autism and Alzheimer’s Rates Differ by Gender

Autism is more of a risk for boys than girls by a factor of four boys for every one girl or three boys for every one girl diagnosed with autism depending on the type of study and diagnostic criteria. There is some speculation that autism in girls presents with less obvious symptoms than in boys. Girls with autism may have less repetitive behavior and be able to fit in socially better than boys with autism and may have less obvious focus on one main topic of interest. (1)

At the other end of the age spectrum females have a greater rate of Alzheimer’s Disease than males. (13)

The difference has been shown to be significant, not just a difference in diagnostic criteria. Estrogen is a female hormone that may be protecting girls from the risk of developing autism but then in menopause is no longer protecting older females from the risk of developing Alzheimer’s Disease. Patients with Autism and Alzheimer’s have been shown to have a tendency to have increased amounts of protein clusters (amyloid beta) in the brain which in normal health would be cleared away. An animal based study found a genetic strain of mice with a clear gender and age difference. Young male mice developed autism like symptoms and older female mice developed Alzheimer’s like symptoms.

A different study found a gender difference in the amount of a protective protein (ADNP) in young male mice with autism like symptoms and older female mice with Alzheimer’s like symptoms. (6) Complete lack of the protective protein leads to very early death with neural tube defects in animal studies.  (7) The neuroprotective protein (ADNP) seems to promote autophagy (our body’s recycling method, it makes us more energy efficient and helps detoxify/remove old cells or material such as the beta-amyloid protein for reuse, read more:  14) and the deficit of it may also be involved in schizophrenia. (8) The protein is involved with control of the dendritic branching of brain cells which is typically found to be  different in children with autism. The protein also plays a role in regulating over 400 genes involved in embryo development including ApoE and the tau protein which is found to collect in the brains of patients with Alzheimer’s Disease in addition to beta-amyloid protein. (9)

The role of apoE involves membranes, cholesterol, cannabinoid receptors and lipid rafts – chemistry geeks have fun, three dimensional drawings and a discussion of cholesterol within the brain and its role in several neurodegenerative diseases is available online in full text, the brain includes 25% of the body’s cholesterol even though the brain only accounts for 2% of the total body weight, on average. (10).  A briefer description of the role apoE plays in the brain and with estrogen and Alzheimer’s risk is available with a discussion of the gene differences that are known to increase but not guarantee risk of developing Alzheimer’s Disease. (11)

Disclosure: a genetic screening suggests I do have one of the higher risk differences in the ApoE gene. (rs2254958)

Strategies to help increase autophagy may help reverse some of the risk factors associated with reduced ApoE/reduced ADNP levels –

  1. vigorous exercise,
  2. a ketosis promoting, low carbohydrate diet, regularly or occasionally,
  3. fasting for a day or a partial day occasionally. (14)

The activity of the apoE protein on other genes can be affected by cannabinoids, too little cannabinoids may be a problem or too much.

The take home point – magnesium and adequate cannabinoids seem to be involved in helping clear the protein clusters during normal health.

  • Nutritional strategies recommended to help prevent Alzheimer’s disease include increasing intake of magnesium. Research has found that low levels of magnesium promoted build up of  beta amyloid protein while high levels of magnesium promoted breakdown of the misshapen proteins.

“Lab studies show that magnesium modulates enzymes involved in amyloid beta production; at low levels, magnesium favors amyloid beta buildup, while at higher levels it favors amyloid beta breakdown.101,102″ [2]  (from a  2014 post)

Certain genetic conditions and chronic health conditions or older age can make the body less able to make cannabinoids endogenously/internally. External sources of cannabinoids have been shown to be helpful for clearing the protein clusters involved in Alzheimer’s Disease. (https://www.sciencedaily.com/releases/2016/06/160629095609.htm)

An underlying infection with bacteria or yeast may be involved in the buildup of the protein clusters as they have a protective effect against some types of infection, so addressing low grade chronic infection may be needed to help stop the over production of the amyloid beta protein clusters in addition to providing adequate magnesium and cannabinoids. Note that there are non-euphoric cannabinoids and legal food sources in addition to medical marijuana. Pumpkin seeds are a good source, $200 billion per year is estimated to be spent on Alzheimer’s care annually at our current rate of the disease prevalence – that would buy a lot of pumpkin seeds. (15 )

That article also mentions that 192 pharmaceutical chemicals have been anticipated and tested in hope of a cure or effective treatment for Alzheimer’s Disease but which have ultimately not been found to be successful. One hundred and ninety two chemicals tested, one hundred and ninety two chemicals found ineffective – magnesium and cannabinoids however have been found effective at helping the body to naturally break down the tau and  beta-amyloid protein clumps that lead to brain damage and later symptoms of dementia in Alzheimer’s Disease and a few other neurological conditions including traumatic brain injuries and autism. (15 ) (links re tau/amyloid in autism & Alzheimers) (links re tau/amyloid protein in traumatic brain injury)

Ibuprofen is a pharmaceutical that is no longer covered by a patent and it has been found to be beneficial in protecting against Alzheimer’s Disease (link: 16) and the underlying reason is likely that ibuprofen prevents the break down of cannabinoids (17)(Search term: “ibuprofen prevents break down of cannabinoids”) – but you need cannabinoids first and some people might no longer be able to make them after a certain age or state of health or may never have been able to make them as well due to genetic differences.

So celebrate protecting your brain today by eating pumpkin seeds, cardamom spice, the herb rosemary, chocolate, or leafy green vegetables. – and the brightly colored tiny inner part of a piece of corn that you can see when eating corn on the cob is also a good source.

  • The misshapen tau/amyloid-beta proteins have a protective effect against bacteria and the yeast Candida albicans so a chronic lowgrade infection may be an underlying cause of the accumulation of beta amyloid placques. [3] [4] (from a  2014 post)

There are many more legal food sources of cannabinoids or a precursor available, a longer list is included below. The progression of Alzheimer’s Disease can take twenty years before symptoms are obvious, so getting an early start on protecting against the tau/beta-amyloid protein build-up makes sense to me (Disclosure, I have a direct family history of the disease in older relatives and a genetic screening suggests that I am more at risk, so I am biased towards preventing the disease in my own brain or other family members.)

Phospholipids are part of cannabinoids and other phosphorus containing nutrients are important in energy production. The phospholipids and cannabinoids are important for the health and function of skin and other membranes lining cells and organs, and/or if you care more about having a good hair day than whether you might get Alzheimer’s Disease in several decades, then the phospholipids are also important for hair growth: *The phospholipid mixture in this animal-based study was applied on the skin surface for hair loss associated with inflammatory skin dermatitis: (18)

(Additional Discloure: I am also genetically at risk for Male Pattern Baldness which became visibly apparent when my autoimmune disease was more severe, however with my switch to phospholipid rich foods my hair has since grown back and my autoimmune condition is in remission as long as I continue with my new health habits).

Other nutrients including the B vitamins, vitamin E, and zinc are also important for healthy hair growth (read more) but many of the following list would also be good sources of B vitamins, vitamin E, zinc and other trace minerals and essential omega 3 and omega 6 fatty acids. Pumpkin seeds are a good vegetarian source of zinc, otherwise the mineral is more commonly available in meats.

  • Food Sources of Phospholipids and other phospho-nutrients: Hemp seed kernels and oil; Artemisia turanica/wormwood leaf; amaranth seed; asparagus; avocado fruit or the inner kernel, dried and powdered; beans/legumes; cardamom seeds and powder; carrots; celery stalks and leaves; cocoa beans and cocoa powder, baker’s chocolate, dark chocolate and to a lesser amount milk chocolate and chocolate syrup; coconut; cumin seed/powder; fennel seed, flax seed, pine nuts; sesame seeds, pumpkin seed kernels, squash seeds; butternut squash and pumpkin; gingko leaf; grapefruit and orange juice with the pulp; Jerusalem artichoke (this is a root vegetable rather than a green artichoke); lettuce, spinach and mustard leaves and other leafy green vegetables and herbs; nuts/peanuts, cashews, walnuts; oats; okra seeds; onion root, leek leaves, garlic;  parsnip root; pomegranate seeds and pomegranate peel extract;rice, white or brown but the bran is the best source; rosemary; sorghum;  sweet potato or yam; buckwheat (a seed botanically that is not wheat and is gluten free); wheat. (G.26)

That topic took a walk around the block and picked some daisies along the way but the important message might be that eating well and exercising regularly may promote healthy hair, a fit body right now while helping maintain healthy brain function into the future. Genetic susceptibility may be involved in the rate of young males with autism and older females with autism and prevention might include more magnesium and phospholipid rich foods in the diet with a diet that is moderate in carbohydrates and regular vigorous exercise to promote autophagy to help promote the natural recycling of tau and beta-amyloid protein that tends to accumulate in the brains of people with autism and Alzheimer’s Disease. Lack of ADNP protein may lead to lack of ApoE or a genetic difference may cause reduced ApoE and the deficiency may lead to a reduced level of autophagy.

Fasting for a day or partial day occasionally or a low carbohydrate diet, even just a diet balance as low as 30% of calories, and vigorous exercise are three natural ways that may help promote autophagy – our body’s natural method for removing and reusing old cellular material. (14) Those strategies might help a woman with Alzheimer’s risk but for an infant or toddler may need to be adapted to simply allowing vigorous, safe play, and a diet that with a greater percentage of healthy fats than average. The list of phosphonutrient rich foods are generally healthy and safe for prenatal diets or other stages of life and would likely promote a fit body and healthy hair for a person of any age and gender – and what is good for the hair is good for other membranes throughout the body and is also good for the brain. The hair is a protein that is a modified form of skin tissue and so is fingernail protein – beauty is more than skin deep.

Some daisies.

Disclaimer: Opinions are my own and the information is provided for educational purposes within the guidelines of fair use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes. Thanks.

  1. Sarah Deweerdt,  Estimate of autism’s sex ratio reaches new low, April 27, 2017,  spectrumnews.org https://www.spectrumnews.org/news/estimate-autisms-sex-ratio-reaches-new-low/ 
  2. Liam Hawkins, Nutritional Strategies and Alzheimers, March 2013 lifeextension.com, http://www.lifeextension.com/magazine/2013/3/Nutritional-Strategies-to-Combat-Alzheimers/Page-02
  3. Lisa Conrick, What is Causing Beta-Amyloid Production in Alzheimer’s and Autism?, Oct. 23, 2012, ageofautism.com, http://www.ageofautism.com/2012/10/what-is-causing-beta-amyloid-production-in-alzheimers-and-autism.html
  4. Molnar Mark, Alzheimer’s Disease Emerging Role of Infection,  http://miklossy.ch/
  5. Why women have more Alzheimer’s disease than men: gender and mitochondrial toxicity of amyloid-beta peptide. J Alzheimers Dis. 2010;20 Suppl 2:S527-33. https://www.ncbi.nlm.nih.gov/pubmed/20442496
  6. Activity-dependent neuroprotective protein (ADNP) exhibits striking sexual dichotomy impacting on autistic and Alzheimer’s pathologies. Transl Psychiatry. 2015 Feb 3;5:e501. https://www.ncbi.nlm.nih.gov/pubmed/25646590
  7. Shmuel Mandel, Gideon RechaviIllana Gozes, Activity-dependent neuroprotective protein (ADNP) differentially interacts with chromatin to regulate genes essential for embryogenesis. Developmental Biology, Volume 303, Issue 2, 15 March 2007, Pages 814-824. https://www.sciencedirect.com/science/article/pii/S0012160606013960

  8. Shlomo Sragovich, Avia Merenlender‐Wagner, Illana Gozes, ADNP Plays a Key Role in Autophagy: From Autism to Schizophrenia and Alzheimer’s Disease. BioassaysVolume39, Issue 11, November 2017, Pages 1700054 https://onlinelibrary.wiley.com/doi/pdf/10.1002/bies.201700054

  9. Gozes Illana, (2015) Activity-dependent neuroprotective protein (ADNP): from autism to Alzheimer’s disease. SpringerPlus. 4. L37. 10.1186/2193-1801-4-S1-L37.  https://www.researchgate.net/publication/282802744_Activity-dependent_neuroprotective_protein_ADNP_from_autism_to_Alzheimer’s_disease
  10. M Maccarrone, G Bernardi, A Finazzi Agrò, and D Centonze, Review: Cannabinoid receptor signalling in neurodegenerative diseases: a potential role for membrane fluidity disturbance. British Journal of
    Pharmacology, Themed Issue: Cannabinoids in Biology and Medicine, Part I, Nov. 16, 2010. http://files.iowamedicalmarijuana.org/petition/2012/bjp-aug-2011-1379-1390.pdf
  11. Hilary Lampers, ND, 5 Reasons to Know Your APOE:  Understanding Your Alzheimer’s Disease Risk. June 13, 2016 thenatpath.com
  12. http://thenatpath.com/body/5-reasons-to-know-your-apoe/
  13. Maxwell A. Ruby, Daniel K. Nomura, Carolyn S. S. Hudak, Lara M. Mangravite, Sally Chiu, John E. Casida, and Ronald M. Krauss, Overactive endocannabinoid signaling impairs apolipoprotein E-mediated clearance of triglyceride-rich lipoproteins. Proc Natl Acad Sci U S A. 2008 Sep 23; 105(38): 14561–14566. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2567196/

  14. Nick English, Autophagy: The Science-Backed Way to Cleanse Your Body, July 4, 2016, greatist.com, https://greatist.com/live/autophagy-fasting-exercise
  15. Stuart W Titus, PhD, Dr. Titus’ Insights: Alzheimer’s Research and the Work of Dr. Schubert, Aug. 5, 2016, medicalmarijuanainc.com,  https://www.medicalmarijuanainc.com/dr-titus-insights-alzheimers-research-work-dr-schubert/
  16.  Neuroscientists say daily ibuprofen can prevent Alzheimer’s disease., March 26, 2018, sciencedaily.com,   https://www.sciencedaily.com/releases/2018/03/180326140239.htm

  17. K. D. Rainsford, IbuprofenDiscovery, Development and Therapeutics. 
    John Wiley & Sons, June 25, 2015, page 134, https://books.google.com/books?id=CAcLCgAAQBAJ&pg=PA134&lpg=PA134&dq=ibuprofen+prevents+break+down+of+cannabinoids&source=bl&ots=oJ_cjSrWXr&sig=yQgwSrdZOkA1MNDkbf7EF7waItY&hl=en&sa=X&ved=0ahUKEwjf7ZKPrcnaAhVlneAKHeDyAuAQ6AEIlQEwCA#v=onepage&q=ibuprofen%20prevents%20break%20down%20of%20cannabinoids&f=false
  18. Seong-Hyun Choi, Jeong-Su Moon, Byung-Suk Jeon, Yeon-Jeong Jeon, Byung-Il Yoon, and Chang-Jin Lim, Hair Growth Promoting Potential of Phospholipids Purified from Porcine Lung Tissues. Biomol Ther (Seoul). 2015 Mar; 23(2): 174–179. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4354319/
  19. ADNP related syndrome FTNW, *lack of ADNP genetically leads to reduced muscle tone and can cause eating problems in children. https://www.rarechromo.org/media/information/Chromosome%2020/ADNP%20related%20syndrome%20FTNW.pdf

Cannabinoids and Alzheimer’s Disease

The body needs carbohydrates, proteins, fats, vitamins, trace minerals, and phospholipids and many other chemicals that can be made within the body if it is well-nourished and has average genetic and youthful abilities. That is a lot to expect from a body and a nutritionist can be a helpful expert to have on your team.

It is 420 day – a typical day in some circles to discuss or celebrate cannabinoids – so some celebratory news – cannabinoids have been shown to help breakdown the clumps of protein that lead to Alzheimer’s Disease – and the good news from my research for everyone who prefers to keep their distance from cannabis/marijuana itself is that cannabinoids are part of cell membranes and can be found in many foods in small quantities and in a few foods in larger quantities.   https://www.medicalmarijuanainc.com/dr-titus-insights-alzheimers-research-work-dr-schubert/ – According to this article $200 billion is spent on Alzheimer’s Disease care every year. That would buy a lot of pumpkin seeds.

The article also includes the number 192 – the number of pharmaceutical chemicals that have been anticipated and tested in hope of a cure or effective treatment for Alzheimer’s Disease that have ultimately not been successful. One hundred and ninety two chemicals tested, one hundred and ninety two chemicals found ineffective – cannabinoids however have been found effective at helping the body to naturally break down the tau and  beta-amyloid protein clumps that lead to brain damage and later symptoms of dementia in Alzheimer’s Disease and a few other neurological conditions including traumatic brain injuries and autism. (links re tau/amyloid in autism & Alzheimers) (links re tau/amyloid protein in traumatic brain injury)

So I personally don’t want to wait for number 193, 194, 195, 196, 197, 199 and 200 in hopes that a patent protected chemical treatment can be found to substitute for our body’s natural abilities – I would rather eat pumpkin seeds and other phospholipid rich foods today. Ibuprofen is a pharmaceutical that is no longer covered by a patent and it has been found to be beneficial in protecting against Alzheimer’s Disease (link: https://www.sciencedaily.com/releases/2018/03/180326140239.htm) and the underlying reason is likely that ibuprofen prevents the break down of cannabinoids (book excerpt)(a variety of links) – but you need cannabinoids first and some people might no longer be able to make them after a certain age or state of health or may never have been able to make them as well due to genetic differences.

So celebrate protecting your brain today by eating pumpkin seeds, cardamom spice, Rosemary, chocolate, or leafy green vegetables. – the brightly colored tiny inner part of a piece of corn that you can see when eating corn on the cob is also a good source.

Another source of a variety of beneficial phytonutrients that we tend to discard instead of eating is the white part around oranges and grapefruit – don’t worry about trimming it all away because it is good for us and mild in flavor. The tougher peel also has beneficial nutrients but it is strongly flavored and can be used in tiny amounts to add a lemony flavor to foods, either freshly grated as lemon or orange zest, or it can be purchased in Middle Eastern grocery markets as powdered dried lemon or lime (Citron vert Seche moulu or Limon seco molido, or Arabic, see example). For maximal flavor add the dried lemon or lime after cooking at the table. The flavor rich terpenes that give the lemony flavor can be effected by long cooking times. The boiling point of limonene is 348.8°F.

Disclosure: This information is being provided for educational purposes within the guidelines of Fair Use. While I am a Registered Dietitian is is not intended to provide individualized health care guidance. Please seek an individual health care professional for the purpose of individualized health care guidance. Thanks.