Receptor Decoy Raises Risk of Alzheimer’s—But Only in Women

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TLS
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Receptor Decoy Raises Risk of Alzheimer’s—But Only in Women

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An interesting article was published this week in ALZForum under News.
https://www.alzforum.org/news/research- ... only-women

In the July 15 Nature Aging, they reported that female APOE4 carriers who had high levels of sST2 in their blood and cerebrospinal fluid were likelier to have AD. They had more amyloid plaques and more shrunken brains. A Mendelian randomization analysis suggested that a variant that suppresses sST2 expression slows brain atrophy and cognitive decline, and reduces AD risk. These findings may explain some of the heterogeneity of AD risk between the sexes, and implicate a new pathway in microglial dysfunction.

All told, women APOE4 carriers whose blood and CSF sST2 levels are high have impaired microglia and higher odds of AD, while those with the rs1921622 variant are somewhat protected.

Why the effects of IL-33/ST2L signaling are linked to sex and APOE genotype is unclear. Perhaps testosterone, which ramps up IL-33/ST2 signaling, protects men from the deleterious effects of sST2? As for APOE4, the authors think that IL-33/ST2 signaling may control microglial activation differently in people with different APOE genotypes.
apoe 3/4
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SusanJ
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Re: Receptor Decoy Raises Risk of Alzheimer’s—But Only in Women

Post by SusanJ »

Interesting. The full article is at: https://www.nature.com/articles/s43587-022-00241-9

This snp is on the IL1RL1 gene, and a quick look through the NIH and Snpedia info shows that IL1RL1 is influenced by the Vitamin D pathways.

And if you are wondering if you have the get-out-of-jail variant, the abstract notes "Subsequent single-nucleus transcriptomic profiling revealed that the rs1921622 A allele is associated with enhanced microglial activation toward Aβ and lowered Aβ plaque load in female APOE-ε4 carriers with AD."
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