By Gabi Giacomin
Research from Canada in 2006 gave us an insight into the progression of Alzheimer’s Disease (AD) in Down Syndrome (DS). Beta secretase activity, generated by the BACE1 gene, is elevated in DS causing an increase in Amyloid precursor protein (APP) and formation of plaques and tangles of neurons.
This research concluded that BACE1 must be inhibited to reduce the progression of Alzheimer’s in DS.
Fast forward to 2015, Hugel and Jackson from RMIT Melbourne, Australia publish their research on Alzheimer’s prevention. Their article “Polyphenols for the Prevention and Treatment of Dementia Diseases” stresses the importance of diet and Polyphenols in the treatment of Alzheimer’s in the typical population. While their research isn’t directed at people with T21, the gene’s they are targeting in their research – APP and BACE1 are the same ones we are.
So, what do they suggest?
Herbal polyphenols such as EGCg are potent inhibitors of Amyloid Precursor Protein (APP). Quercetin inhibits BACE1 activity and plaque formation. EGCg, Resveratrol, Curcumin inhibit Beta Amyloid tangles and plaque, reducing neurodegeneration. Curcumin (responsible for low rates of AD in India) inhibits fibrin formation, binds to plaque and reduces Amyloid levels in vivo. Resveratrol has protective effects on cognition.
Each of these ingredients are part of a Nutrigenetic Program for Down Syndrome, which I recommend to my clients.
Links to articles on BACE1, BACE2, APP and Down Syndrome published between 2006 and 2016:
Protein expression of BACE1, BACE2 and APP in Down Syndrome brains.
Increased BACE1 maturation contributes to the pathogenesis of Alzheimer’s disease in Down syndrome.
Upregulation of SET expression by BACE1 and its implications in Down syndrome.
β-Secretases, Alzheimer’s Disease, and Down Syndrome
Changes in BACE1 and BACE2 Expresssion in Alzheimer’s Disease and Down Syndrome
“Herbal polyphenols are known to also modulate Aβ production by stimulating the α-secretase and inhibiting the β-site amyloid precursor protein cleaving enzyme-1 (BACE1), γ-protease pathways. (−)-Epicatechin, epigallocatechin are potent inhibitors of amyloid precursor protein processing (APP). Some phenolics show both, a strong inhibition of APP-Aβ generation and anti-amyloidogenic binding (Hügel and Jackson, 2012). The flavonoids quercetin and myricetin (Figure) inhibit BACE1 activity, dose-dependently inhibit amyloid fibril formation with myricetin > quercetin > catechin = epicatechin. Similarly, EGCG, resveratrol, curcumin, oleuropein, pentagalloylglucose inhibit β-amyloid misfolding and aggregation by forming nontoxic complexes with the peptide, they also have other benefits against the onset of neurodegeneration. EGCG directly interacts with β-sheet structures in amyloid fibrils leading to an decrease in the binding of Aβ to the fluorescent dye thioflavin T and promotes the assembly of large, spherical oligomers into safe species, unable to seed fibrillogenesis; remodels Aβ mature fibrils into smaller, amorphous protein aggregates by direct binding to the β-sheet-rich aggregates and mediating a conformational change without generating potentially toxic oligomers (Ehrnhoefer et al., 2008). Curcumin is the main constituent of the spice turmeric, whose extensive use apparently accounts for the lower prevalence of AD in the Indian population. In vitro curcumin inhibits fibril formation and also destabilizes preformed fibrils, binds to plaques and reduces amyloid levels in vivo. Curcumin and resveratrol bind to the N-terminus (residues 5−20) of Aβ42 monomers. Many in vitro studies have demonstrated the multiple potential therapeutic effects of resveratrol, found in herbs, red wine, but its in vivo efficacy is controversial. The beneficial effects of resveratrol may contribute to its protective effects on cognitive function, however the volume of red wine to be consumed for resveratrol therapy is not practicable.”
https://www.ncbi.nlm.nih.gov/pubmed/16816111
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4705783/
