Saturday, April 9, 2022

Genes, genes, and more genes...

In Beating the Dementia Monster, we said that about 30 genes had been identified that caused or contributed to the development and/or advance of Alzheimer's disease.  These genes, of course, vary in how strongly they influence the disease.  The gene for the amyloid precursor protein and the two presenilin genes are almost certain to cause the rare but devastating young onset form of the disease.  But 23&Me will test you for the ApoE4 gene which is correlated with many cases of the more common old-onset form of the disease.

In addition to that 30, we noted back in July that six more had been identified.  But is that all?  My sister recently pointed me to a story in CNN about research reported in Nature Genetics regarding the identification of 42 more.  The researchers also developed a scorecard to predict someone's probability of developing Alzheimer's disease or for advancing from mild cognitive impairment to dementia based on which variants of these genes you may carry.

As we noted in our July posting, the genes we discussed don't explicitly cause Alzheimer's disease, but rather they create a favorable environment in the brain for the disease to start and/or advance.  Most often, this is an environment favorable to inflammation.  Lifestyle changes then don't fight the proteins originating with the genes but rather attempt to modify the environment they create.

This new research is interesting in that it finds a broader influence of genetics and the development of Alzheimer's disease.  In Beating the Dementia Monster, we discussed the possible role of microglia in the advance of the disease.  Microglia are the specialized immune cells peculiar to the brain and spine that operate independently from the immune system in the rest of the body.  The microglia help clean up the trash in the brain, such as the amyloid plaques and tau tangles that are central to the disease process.  We said it may be that as we age, the microglia become less effective.  This new research correlated some genes associated with microglia with Alzheimer's disease.  The thinking is that some genes may affect how well the microglia cells function.

Genes specify the design of the proteins in the cell, and over time, mutations result in variations in the design.  This creates variations in how the proteins do their jobs.

The more deeply the researchers got into the role that these many genes play in the advance of the disease, the more impressed they were with the incredible complexity of how the genes influence the disease.  This led them to develop a scorecard for evaluating someone's risk of developing Alzheimer's disease based on which variant of all these genes they carry.  They wrote, "Based on this evidence, we developed a systematic gene prioritization strategy that yielded a total weighted score of between 0 and 100 for each gene."  Their analysis identified 31 tier 1 (higher influence) genes and 24 tier 2 (lower influence) genes for weighting purposes.

As we said in Beating the Dementia Monster, carrying the ApoE4 gene does not guarantee that you will develop Alzheimer's disease.  The scorecard goes on to quantify the risk for someone carrying this famous gene when the person's genome includes a mix of the other genes.

So to me, this scorecard is a remarkable development.  I wonder if 23&Me will adopt it.  I'm sure that, before 23andMe adopts it, the long-term care insurance companies will jump on it to set premiums and screen out those they won't want to insure.

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