Target Causes of Alzheimer’s Disease (AD)

In people with Alzheimer’s disease, changes in the brain begin many years before the first sign of memory problems. They include:

1. The gradual accumulation of beta-amyloid peptides

2. The gradual accumulation of tau proteins

Both of these form plaques and tangles that are considered hallmarks of the disease, and can now be seen with cutting-edge imaging techniques such as:

AD Predictive Beta Amyloid

 

 

 

 

 

 

 

 

PET scan images show distribution of tau (top panel) and beta-amyloid (bottom panel) across a brain with early Alzheimer’s disease. Red indicates highest levels of protein binding, dark blue the lowest, yellows and oranges indicate moderate binding.
Credit: Brier et al., Sci Transl Med

3. Brain Tissue inflammation, with an increase in beta- and gamma-secretase enzymes. 

While medications have been disappointing, there are a number of  foods and supplements that show promise in pre-clinical studies: But, unfortunately, one would have to take these early in life, when the AD abnormalities start, and approximately 20 years before the debilitating symptoms.

Our goal is to reduce causes of Alzheimer’s Disease–Too much:

Amyloid Beta (Abeta);

Tau Protein;

Beta-Secretase and Gamma-Secretase enzyme activity: 

A. Fish, fish oil, and the DHA component of fish oil works through several pathways:

1. Reduces Abeta and the inflammatory prostaglandin E2. 

2. Reduces levels of Tau protein. This is the first treatment described that reduces tau pathology.

3. Reduces Levels of the inflammatory enzyme Gamma-Secretase

B. Green Tea reduces levels of inflammatory Beta-Secretase (Bioorganic & Medicinal Chemistry Letters Volume 13, Issue 22, 17 November 2003, Pages 3905-3908 Green tea catechins as a β-Secretase inhibitor lSo-YoungJeon) and may improve AD by other mechanisms. (a 2015 paper in the Journal of Azheimer’s Disease demonstrated that EGCG, especially in conjunction with exercise, might help minimize the impact of Alzheimer’s.)

C. Berberine reduces β-amyloid pathology, gliosis, and cognitive impairment in an Alzheimer’s disease transgenic mouse model. Durairajan SS et al, Neurobiol Aging. 2012 Dec;33(12):2903-19

D. Niacinamide reduces levels of Tau protein in an animal model: “These preclinical findings suggest that oral nicotinamide may represent a safe treatment for AD”

***Studies are mixed regarding the use of NSAIAs for the ongoing brain inflammation.

Other Possible helpful Natural Products:

Berries: Berries contain polyphenols, a type of antioxidant which helps stop inflammation and allows brain cells to work better. A Tufts University study found that berries can reverse slow-downs in the brain’s ability to process information.

Leafy Vegetables: Women in their 60s who ate more leafy vegetables over time did better than their non-greens-eating counterparts on memory, verbal, and other tests.

Vitamin C: New studies show that high levels of vitamin C may help with dementia prevention.

Tumeric, with active ingredient Curcumin, and Vitamin D: Can help prevent Alzheimer’s. In one such study, researchers from UCLA found that vitamin D3, taken with curcumin, may help the immune system to get rid of the amino acids that form the plaque in the brain in Alzheimer’s Disease.

Coffee: Researchers from the University of South Florida and University of Miami found that people older than 65 who drank three cups of coffee a day (i.e. had higher blood levels of caffeine) developed Alzheimer’s disease two to four years later than their counterparts with lower caffeine levels, and that caffeine had a positive impact even in older adults who were already showing early signs of Alzheimer’s

Dark Chocolate: In an Italian study, older adults who had mild symptoms of dementia drank cocoa with high, medium and low amounts of flavonoids. Those who consumed high amounts outperformed those who consumed low doses on cognitive tests.

Acetyl-L-carnitine in the treatment of early stages of Alzheimer’s disease and vascular dementia. Gavrilova SI et al, Zh Nevrol Psikhiatr Im S S Korsakova.  2011;111(9):16-22.

Ginkgo: In a placebo-controlled, double-blind randomized trial published in the Journal of the American Medical Association, not only did Gingko biloba stabilize Alzheimer’s disease, but in many of the subjects there was an actual improvement noted in various standardized psychological tests

Galantamine stimulates nicotinic receptors and may be a strategy for Alzheimer’s. Nicotine promotes the transthyretin (TTR) gene, whose product has been shown to bind to amyloid  (A) protein and prevent A aggregation: (Rationale for Combination Therapy With Galantamine and Memantine in Alzheimer’s Disease G. T. Grossberg, K. R. Edwards, and Q. Zhao J. Clin. Pharmacol., July 1, 2006; 46(suppl_1): 17S – 26S)

 

APPENDIX:

J Neurosci. 2008 Nov 5;28(45):11500-10, Green KN et al

Nicotinamide restores cognition in Alzheimer’s disease transgenic mice via a mechanism involving sirtuin inhibition and selective reduction of Thr231-phosphotau.

Memory loss is the signature feature of Alzheimer’s disease, and therapies that prevent or delay its onset are urgently needed. Effective preventive strategies likely offer the greatest and most widespread benefits. Histone deacetylase (HDAC) inhibitors increase histone acetylation and enhance memory and synaptic plasticity. We evaluated the efficacy of nicotinamide, a competitive inhibitor of the sirtuins or class III NAD(+)-dependent HDACs in 3xTg-AD mice, and found that it restored cognitive deficits associated with pathology. Nicotinamide selectively reduces a specific phospho-species of tau (Thr231) that is associated with microtubule depolymerization, in a manner similar to inhibition of SirT1. Nicotinamide also dramatically increased acetylated alpha-tubulin, a primary substrate of SirT2, and MAP2c, both of which are linked to increased microtubule stability. Reduced phosphoThr231-tau was related to a reduction of monoubiquitin-conjugated tau, suggesting that this posttranslationally modified form of tau may be rapidly degraded. Overexpression of a Thr231-phospho-mimic tau in vitro increased clearance and decreased accumulation of tau compared with wild-type tau. These preclinical findings suggest that oral nicotinamide may represent a safe treatment for AD and other tauopathies, and that phosphorylation of tau at Thr231 may regulate tau stability

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