The Many Effects Of The APOE4 Variant

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TheresaB
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The Many Effects Of The APOE4 Variant

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Anyone else been following Dr William Hazeltine's* multi-part series Reimagining Alzheimer's in Forbes?
*(researcher, author, former professor at Harvard Medical School, known for work on cancer, HIV/AIDS, genomics and COVID-19)

He began part 5 of his series in November by saying it was his last installment. Then a paper APOE4 impairs myelination via cholesterol dysregulation in oligodendrocytes was published shortly thereafter in Nature on 16 Nov 2022.

So he added part 6 Reimagining Alzheimer’s (Part 6): The Many Effects Of The APOE4 Variant
focusing on APOE4 explaining the information from that study in more digestible form.

from his paper
Studies conducted by a team at the Massachusetts Institute of Technology suggest that the E4 variant of the APOE gene disrupts how fat molecules are processed in the brain. It appears that the disruption of these fat molecules could be the fundamental reason why those that contain the E4 variant are more likely to develop Alzheimer’s symptoms including brain cell death, memory issues, and cognitive decline.
The researchers found that the E4 variant significantly affected the expression of genes related to intracellular activities. Interestingly, this included increased expression of genes associated with inflammation and other immune-related pathways. Many studies have recently pointed to inflammation as a core feature of Alzheimer’s disease.
and
These studies suggest that increased inflammation in Alzheimer’s patients may be linked to the development of both amyloid plaques and tau tangles and may exacerbate the cognitive symptoms of Alzheimer’s.
That APOE4s are more susceptible to inflammation is not new, but this is further reinforcement of this issue with us.
-Theresa
ApoE 4/4
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