Walhovd KB, Fjell AM, Sørensen Ø, Mowinckel AM, Reinbold CS, Idland AV, Watne LO, Franke A, Dobricic V, Kilpert F, Bertram L, Wang Y. Genetic risk for Alzheimer disease predicts hippocampal volume through the human lifespan. Neurol Genet. 2020 Oct;6(5):e506. Epub 2020 Sep 8 PubMed.
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Cardiff University
I was interested in this finding, showing that polygenic risk for AD is associated with a reduction in hippocampal volume throughout the lifespan. The most salient observation of this study is that this small but significant effect is seen in the very young.
What does this mean? This could be the manifestation of cognitive reserve. However, one could further speculate that the mechanisms which underlie Alzheimer’s polygenic risk could also underlie the processes that grow and/or maintain the capacity of the hippocampus.
Could it be that these processes also affect cognitive capacity and in turn IQ, which are known to be negatively associated with AD later in life? One may also speculate that these shared processes may implicate the role of immunity, and possibly that of microglia, in the development of both cognitive capacity in early life and the propensity to neurodegeneration later in life. These are intriguing possibilities which will need further work to unpick.
View all comments by Julie WilliamsWith respect to the similarity of "each copy of APOE4" data and "all-inclusive PGS" data, and the analogy between the immune response of ages 4-20 and 70-95, I wonder whether the middle age group really does not have an intrinsic factor in its immune system that withholds the expression in microglia and astrocytes. This might also impede hippocampus tissue atrophy, rather than merely the fewer number of participants in that group accounting for the outcome.
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