Peter on Alzheimer’s disease prevention and the latest on APOE4

This clip is from episode #202, Peter on nutrition, disease prevention, sleep, and more, originally released on April 11, 2022.

Show Notes

Alzheimer’s disease: genes that modify risk associated with the APOE4 variant [40:15]

Changes in thought related to Alzheimer’s disease: When it comes to Alzheimer’s disease, Peter’s focus on genes outside of APOE is now pretty significant

• It turns out that there are a lot of genes that seem to modify the risk of APOE
• APOE has three subtypes, e2, e3, and e4
• Everyone has a pair meaning there are six possible combinations
• The fourth isoform (e4) is the high risk one
• If you’re a e2/e4 it seems to, more or less, be a wash with maybe slight increase in risk
• The e3/e4 seems to be associated with about a 2x-3x increase in risk in Alzheimer’s disease
• The e4/e4 probably has about an 8x-12x increase in risk
• But even though everything above is true at the population level, it doesn’t explain what happens at the individual level 
• There are some individuals who walk around with e4/e4 who don’t seem to get Alzheimer’s disease or if they do, they get it very late in life 

Genes that modify the risk of the e4 variant

• It turns out that there are a bunch of other genes that we’re now starting to understand, modify the risk of e4 (some genes make it more significant, some genes make it less)
• So there are certain haplotypes of the TOMM40 gene that amplify risk
• There are certain mitochondrial haplotypes that amplify risk
• One of the most exciting genes is the Klotho modifier
  • KL-VS is the modified snip of klotho that actually seems to erase all of the downside of APOE4
  • So APOE4 people who have this klotho subtype have baseline risk

Prospects of identifying these genes in individuals

• Unfortunately the ways to measure these other genes, it’s very challenging and we have to do it by brute force today
  • it takes a lot of time and costs a lot of money to take a whole genome sequence and do the search for all of these other subtypes
  • A big step in the right direction here is going to be getting more data and getting those data for less than $20,000 per person.
• When might this be practical to do for people?
  • Probably sooner than 10 years from now
  • This is a solvable problem technically speaking, it’s just about throwing enough dollars at it