Dissection of the polygenic architecture of neuronal Aβ production using a large sample of individual iPSC lines derived from Alzheimer’s disease patients

Conserved cell-type specific signature of resilience to Alzheimer’s disease nominates role for excitatory intratelencephalic cortical neurons

“…KCNMA1 SNPs were found to be associated with age at onset and duration of AD 73 as well as increasing odds ratio of sporadic AD. 74 STXBP1 (Syntaxin Binding Protein) codes for protein MUNC18-1 that interacts with the SNARE complex involved in neurotransmitter release that has recently been found to interact with tau. 75 Another SNARE- related protein, CPLX1, had been previously shown to be associated with cognitive resilience.…”

“…75 Another SNARE- related protein, CPLX1, had been previously shown to be associated with cognitive resilience. 4 Interestingly, mRNA levels of KCNM1 74 and ATP1A1 76 have been reported to be elevated in AD. In our mouse snRNA-seq data, these four genes are expressed in at least 10% of nuclei in both groups of mice, with proportionally more resilient nuclei expressing them, while in nuclei that do express the gene, the average expression between resilient and susceptible groups is similar.…”

CDiP technology for reverse engineering of sporadic Alzheimer’s disease

“…In order to perform a genome-wide gene investigation, it is necessary to prepare population-scale patient data. Therefore, we tackled this issue by establishing iPSCs from more than one hundred AD patients, and defined these iPSCs as the “iPSC cohort” [ 37 ] (Fig. 3 ).…”

“…In this way, we proposed a concept to factorize the complex AD brain pathology into a combination of cell type and related AD phenotypes. Then, we set patient parameter variables, in other words “traits”, for each combination of cell type and phenotype, performed GWAS analysis, and named this scheme “cell GWAS” [ 37 ](Fig. 3 ).…”

Prediction of amyloid β accumulation from multiple biomarkers using a hierarchical Bayesian model

“…However, most cases of AD progress sporadically, and many patients have no family history of AD 2,3 . Thus, the genetic background of sporadic AD has been extensively investigated, revealing the complex genetic architecture of late-onset neurodegenerative diseases [4][5][6][7] .…”