—-
Last week a discovery, published in the journal Science, showed that a high level of an abnormal ‘phosphorylated-tau’ protein triggers brain cells to self-destruct. It also gives a vital clue as to how to stop your brain cells dying with specific vitamins.
When cells become largely dysfunctional, they self-destruct. This process in neurons (brain cells) is called ‘necroptosis’. The recent discovery, made by researchers at the UK’s Dementia Research Institute at University College London (1), showed that an abnormal accumulation of a protein called tau that then becomes phosphorylated, making it tangled and dysfunctional, triggers a specific molecule called MEG3 that triggers brain cell death.
“For the first time we get a clue to how and why neurons die in Alzheimer’s disease. There’s been a lot of speculation for 30-40 years, but nobody has been able to pinpoint the mechanisms. It really provides strong evidence it’s this specific suicide pathway.” researcher Prof Bart De Strooper, from the UK’s Dementia Research Institute. told the BBC.
Even before this, too much phosphorylated-tau (abbreviated to p-tau) interferes with the cell’s energy factories (called mitochondria), potentially leading to brain fatigue. The more p-tau accumulates, the greater a person’s risk for cognitive problems and Alzheimer’s dementia. Also, those with memory decline have been shown to have relatively more p-tau to tau protein.
The critical prevention question is, then, what stops too much of the tau protein from turning into the potentially harmful p-tau and what helps restore p-tau to normal tau protein.
—-
—-
The answer is remarkably simple – a lack of B vitamins and raised blood levels of homocysteine which is an established risk factor for memory decline, measurable in the blood. When levels of B vitamins (B6, B12 and folate) are low, blood levels of homocysteine go up. This activates one enzyme (Cdk5 kinase) that adds the bad ‘p’ to tau and blocks another enzyme (protein phosphatase A2) which removes the dangerous ‘p’ restoring normal tau protein (2)(3). High homocysteine also damages the tiny blood vessels in the brain, leading to ‘mini strokes’ or transient ischemic attacks (TIAs), which further raise levels of p-tau (4). Homocysteine both raises levels of the dangerous p-tau and can also bind to tau (5), further generating the neurofibrillary tangles that then trigger brain cell death.
So, the simplest way to stop the formation of p-tau, and neurofibrillary tangles, and keep your brain healthy, is to keep your plasma homocysteine level below 10 mcmol/L. Half of those above 65 have a level of homocysteine higher than this. The easiest way to lower your homocysteine below 10 mcmol/L is to supplement B6, B12 and folate.
But it’s also good to eat greens and beans that are high in folate. While B12 is only in animal foods – meat, seafood, eggs and milk. While an optimal supplemental intake for a middle-aged person might be 20mg of B6, 10 mcg of B12, and 400 mcg of folate, many older people start to dramatically lose their ability to absorb B12, the absorption of which requires stomach secretions. Antacid ‘PPI’ medication such as omeprazole accelerates this decline, promoting B12 deficiency. And, over four years of use, increases dementia risk by a third (6). Then, as studies show, you might need a lot more B12, such as 500 mcg, to get a little more into your bloodstream, and possibly more supplemental folate, in the region of 500 to 800 mcg.
This is the cheapest, safest and most logical solution to lower p-tau and prevent brain cells from committing suicide. The problem is that these nutrients, invented by nature, cannot be patented. Therefore it is not in the interest of the pharmaceutical industry to research them.
Consequently, drugs are being developed and tested that block the kinase enzyme and activate the phosphatase enzyme (7), which is exactly what the homocysteine-lowering B vitamins do. But, so far, there are no human clinical trials reporting significant benefit.
On the other hand, trials giving these kinds of doses of B6, B12 and folic acid have shown up to a two-thirds slower rate of brain shrinkage (8) and virtually no further memory loss in those with pre-dementia (9).
—-
Thank you for reading!
Food for the Brain is a non-for-profit educational and research charity that offers a free Cognitive Function Test and assesses your Dementia Risk Index to be able to advise you on how to dementia-proof your diet and lifestyle.
By completing the Cognitive Function Test you are joining our grassroots research initiative to find out what really works for preventing cognitive decline. We share our ongoing research results with you to help you make brain-friendly choices.
Please support our research by becoming a Friend of Food for the Brain.
———
References
1 https://www.science.org/doi/10.1126/science.abp9556 Balasu S et al. Science
14 Sep 2023 Vol 381, Issue 6663 pp. 1176-1182 DOI: 10.1126/science.abp9556
2 Smith AD, Refsum H. Homocysteine, B Vitamins, and Cognitive Impairment. Annu Rev Nutr. 2016 Jul 17;36:211-39. doi: 10.1146/annurev-nutr-071715-050947. PMID: 27431367.
3 LiJ-G,ChuJ,BarreroC,MeraliS,Pratico`D.2014.Homocysteine exacerbatesβ-amyloid, tau pathology, and cognitive deficit in a mouse model of Alzheimer’s disease with plaques and tangles. Ann. Neurol. 75:851–63
4 Shirafuji N et al Homocysteine Increases Tau Phosphorylation, Truncation and Oligomerization. Int J Mol Sci. 2018 Mar 17;19(3):891. doi: 10.3390/ijms19030891. PMID: 29562600; PMCID: PMC5877752.
5 Bossenmeyer-Pourié C et al. N-homocysteinylation of tau and MAP1 is increased in autopsy specimens of Alzheimer’s disease and vascular dementia. J Pathol. 2019 Jul;248(3):291-303. doi: 10.1002/path.5254. Epub 2019 Mar 19. PMID: 307349
6 Northuis C, Bell E, Lutsey P, George KM, Gottesman RF, Mosley TH, Whitsel EA, Lakshminarayan K. Cumulative Use of Proton Pump Inhibitors and Risk of Dementia: The Atherosclerosis Risk in Communities Study. Neurology. 2023 Aug 9:10.1212/WNL.0000000000207747. doi: 10.1212/WNL.0000000000207747. Epub ahead of print. PMID: 37558503.
7 Xia, Y., Prokop, S. & Giasson, B.I. “Don’t Phos Over Tau”: recent developments in clinical biomarkers and therapies targeting tau phosphorylation in Alzheimer’s disease and other tauopathies. Mol Neurodegeneration 16, 37 (2021). https://doi.org/10.1186/s13024-021-00460-5
8 Smith AD, Refsum H. Homocysteine, B Vitamins, and Cognitive Impairment. Annu Rev Nutr. 2016 Jul 17;36:211-39. doi: 10.1146/annurev-nutr-071715-050947. PMID: 27431367; see also Jernerén F., et al. Am J Clin Nutr. 2015 Jul;102(1):215-21.
