Do Genes Really Have Much To Do With Alzheimer’s Disease?

Do Genes Really Have Much To Do With Alzheimer’s Disease? about undefined
Genes are the "command centers" of cells. They instruct cells to make specific proteins, which then determine what kind of cell it will be. Genes also control a cell’s construction and operation, as well as assist in cellular repair. Genes are also delicate. Even small changes in a gene (known as "variants" or "mutations") can cause malfunctioning cells, abnormal proteins and an increased risk of developing diseases and chronic conditions. Here’s a surprise for you: Researchers have yet to find a single gene that contributes to Alzheimer’s disease. But they have discovered genetic risk factors that may increase a person’s risk for developing the disease… Keep reading to discover the role genes play in the development of neurodegenerative conditions.

APOE: The "Alzheimer’s" Gene

You may have heard of the apolipoprotein E (APOE) gene as a risk factor for Alzheimer’s disease. It can be found in three variations, known as "alleles." When a person has variation APOE ε4, research shows he or she has an increased risk of developing the disease. It’s possible for a person to have one or two alleles. Having more APOE ε4 increases the risk, and is also associated with onset at an earlier age.1 However, "increased risk" does not mean you will get the disease. There are many cases of a person with the gene not getting Alzheimer’s, and cases where people without the gene do get it. It’s merely a risk factor, like diet or lifestyle.

Microglia and IL1RAP Gene Mutations

Previous studies have shown how chronic inflammation and other conditions can cause the brain’s microglia, the "janitors of the central nervous system," to start working overtime. When this happens, the microglia start attacking healthy tissue and synapses, causing terrible damage to the brain. (Click here for more information about microglia.) Recent research directly implicates microglia in the development of Alzheimer’s disease. A study published in the June 2017 issue of the journal Nature Geneticsfound that variants in three different genes associated with the regulation of microglia boost the genetic risk for the disease.2 Other studies show that older adults carrying a variant of the gene IL1RAP tend to have a greater buildup of beta-amyloid plaques than those without the variant. These findings were consistent regardless of the presence of APOE. The researchers discovered that, in these cases, people had LESS microglia activity, so they weren’t able to clear out cellular debris properly, leading to a pile up of proteins and plaques. Research published in Brain: The Journal of Neurology found that carriers of the gene variant had greater cognitive impairment. Their brains also showed an increased amount of temporal cortex atrophy, brought on by a lower level of microglia activity.3 The scientists who made this discovery believe that by manipulating this gene, it may be possible to prevent or slow Alzheimer’s disease in people who carry this gene variant. There are already medications that target the IL1RAP gene for the treatment of rheumatoid arthritis and other inflammatory conditions, so a pharmaceutical treatment for this aspect of Alzheimer’s disease may eventually be available.

Future Research: Gaining Ground

There are several large-scale research efforts underway regarding gene mutations and Alzheimer’s disease and other types of dementia. The projects regularly test DNA from thousands of volunteers and study participants. One group, the International Genomic Alzheimer’s Project (IGAP) has been working since 2011. From a study of more than 74,000 people, they’ve identified 19 "new regions of interest" associated with the disease.4 With this many scientists studying so much data, there’s reason to hope for progress in understanding this disease. For now, however, I don’t recommend "genetic fatalism" as a good attitude toward Alzheimer’s. Prevention is still the best cure, and as this newsletter tries to show every week, there are many lifestyle factors under our control – food, supplements, sleep, blood sugar, avoiding harmful medications. Don’t forget that many people who have the so-called "Alzheimer’s gene" never get Alzheimer’s. Take care of your body and brain as best you can for a long, healthy life.
  1. AD genetics.
  2. Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease.
  3. GWAS of longitudinal amyloid accumulation on 18F-florbetapir PET in Alzheimer’s disease implicates microglial activation gene IL1RAP.

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