Polygenic risk score of sporadic late‐onset Alzheimer's disease reveals a shared architecture with the familial and early‐onset forms

Abstract

Our analysis confirms that the genetic factors identified for LOAD modulate risk in sLOAD and fLOAD and also sEOAD cohorts. Specifically, our results suggest that the burden of these risk variants is associated with familial clustering and earlier onset of AD. Although these variants are not associated with risk in the eADAD, they may be modulating age at onset.

Genetic risk score modifies the effect of APOE on risk and age onset of Alzheimer's disease

“…Our results are similar to the findings from several recent studies examining the effect of SNP-based PRSs and their joint effect with APOE on AD risk and AAO. [20][21][22][23][24] In a study analyzing 21 AD risk- Although the conclusions from these published studies and our study are similar, the methods used for measuring the cumulative effect of SNPs differed. In these previously published studies, PRSs were not standardized to a general population and therefore difficult to interpret.…”

“…Several recent studies further demonstrated the combined effect of APOE and risk‐associated SNPs on AD risk . This finding has important implications in inherited risk assessment of AD.…”

Advance of sporadic Alzheimer's disease animal models

“…154,155 The disadvantage of this model is lacking the relevant characteristics of AD, such as plaque formation and NFTs. Morimoto et al injected Aβ or Aβ [25][26][27][28][29][30][31][32][33][34][35] fragments alone or in combination with ibotenic acid into the hippocampus of rats. It was found that the neurons in CA1, CA4, and dentate gyrus were largely depleted, as well as the Aβ deposition present around hippocampus.…”

“…156 Laurent et al injected Aβ and Fe 2+ into the brain of rats and observed the elevation of oxidative stress, Aβ deposition, and memory dysfunction. 157 In addition, there are complex models combined with three kinds of factors, such as co-injecting Aβ [23][24][25][26][27][28][29][30][31][32][33][34][35] , AlCl 3 , and TGFβ1 into the lateral ventricle of rats. The decline of memory and learning ability, neuron loss, NFTs deposition, free radical system abnormalities, glial cell proliferation, and neuroinflammation were observed after 1 month.…”

“…Although gene plays a critical role in both, the existence of genetic risk factors of sAD is not enough for developing the disease. Second, fAD is usually associated with early symptoms of onset, while most of the sAD cases present a late onset . Third, patients with fAD generally have greater parietal atrophy, more white matter abnormalities, while patients with sAD overall have more hippocampal volume loss, higher incidence of diabetes, obesity, and circulatory disorders .…”