Alzheimer’s disease is a scary possibility that faces many of us today — whether for ourselves or for aging parents and grandparents.
Currently, 10% of people age 65 or older have Alzheimer’s disease (AD). It is a disease for which prevention needs to start decades before the symptoms appear.[ref]
Genes combine with environmental exposure and lifestyle to determine your risk for Alzheimer’s disease. There are genetic variants that increase your risk for Alzheimer’s disease. Other variants decrease your risk for the disease.
This article focuses on that protective side of the equation, something that many people worried about AD fail to consider.
Most Alzheimer’s research focuses on the accumulation of amyloid-β plaque and the tangled tau fibrils. These proteins lead to the death of neurons in the brain.
Thirty plus years of research and clinical drug trials on amyloid-β have shown very few positive results.
Amyloid-β is a protein formed when enzymes cut the APP (amyloid precursor protein) protein into smaller fragments. Some of the protein fragments move out of the brain. But amyloid-β that isn’t cleared can build up around neurons, forming plaque.
Early-onset or familial Alzheimer’s occurs before the age of 65. Researchers discovered almost 50 mutations in the APP gene that cause early-onset Alzheimer’s.
Not all APP mutations are bad. Researchers discovered an APP mutation that is protective against getting Alzheimer’s. Less than 0.1% of the population carries this rare variant. The mutation is more common in people from Iceland, Norway, and Sweden than the rest of the world.
Check your genetic data for rs63750847 (23andMe v4 only, AncestryDNA):
Researchers connect the APOE gene with Alzheimer’s risk. APOE (apolipoprotein E) is a lipoprotein that transports cholesterol to the neurons. In the brain, APOE binds and clears amyloid-β protein.
There are three different forms of APOE -ε2, ε3, and ε4. APOE ε4 causes a significant increase in the risk of Alzheimer’s. (Check it here, if you want to know.) But the APOE ε2 version decreases the risk of AD.
About 10% of the population carries the APOE ε2 allele, which slows the accumulation of amyloid-beta in the brain.[ref]
Check your genetic data for rs7412 (23andMe v4, v5; AncestryDNA):
In 2017, a research study showed that a variant in the RAB10 gene protects carriers against getting Alzheimer’s disease. The rs142787485 G-allele, found in about 3% of the population, cuts the risk of Alzheimer’s in half. (This is not covered in 23andMe or AncestryDNA data).[ref]
There are also several genetic variants that slightly decrease the risk of Alzheimer’s. Most of these decrease the risk by 10-15%.
Check your 23andMe data for rs8070723 (23andMe v4, v5; AncestryDNA):
Check your genetic data for rs1476679 (23andMe v5 only; AncestryDNA):
Check your genetic data for rs11136000 (23andMe v4, v5; AncestryDNA):
Check your genetic data for rs3851179 (23andMe v4,v5; AncestryDNA):
Lower cholesterol levels may decrease the risk of Alzheimer’s. This protective effect comes from having lower cholesterol throughout life. People who carry certain PCSK9 variants have lower lifetime cholesterol.[ref]
This is something to consider when adopting a ketogenic diet that may cause an increase in cholesterol. Some people argue that there is no need to worry when their cholesterol level rises with a high-fat diet. The link between cholesterol and cardiovascular disease may be questionable. But the link between Alzheimer’s and cholesterol is one to take into consideration as well.
Some researchers are pursuing alternatives to the amyloid-beta theory as the cause of neurodegenerative diseases. A researcher named Dr. Paul Cox has been pursuing the idea that the incorporation of BMA/A (a neurotoxin found in cyanobacteria) into the brain in place of the amino acid serine is causing neurodegenerative diseases such as Alzheimer’s, ALS, and Parkinson’s.
There are clinical trials going on now to determine if supplementing with l-serine will help ALS patients. Here is a good article in Fortune on Paul Cox’s work: Could This Radical New Approach to Alzheimer’s Lead to a Breakthrough?
Whether the serine hypothesis is correct or not remains to be seen. People interested in preventing Alzheimer’s may want to keep an eye out for new research on the topic.