id author title date pages extension mime words sentences flesch summary cache txt cord-102481-obig3mu1 Alić, Ivan “Patient-specific Alzheimer-like pathology in trisomy 21 cerebral organoids reveals BACE2 as a gene-dose-sensitive AD-suppressor in human brain” 2020-01-31 .txt text/plain 10702 533 53 The validity of this prediction was tested by an independent biochemical method (ELISA), by measuring the Aβ-peptide concentrations within the isogenic T21:D21 organoid CM comparison, which showed an increase in absolute concentrations caused by T21 for each Aβ 1-38, 1-40 and 1-42, with no difference in the Aβ 1-42/1-40 ratio between T21 and isogenic D21 lines, mirroring the readout in the absolute levels of IP-MS peaks ( Supplementary Fig. 6 ). Pearson's coefficient showed a high level of colocalisation (>0.55) of both the main substrate (Aβx-40) and its putative degradation product (Aβx-34) with BACE2 in neurons of cerebral organoids, in LAMP2+ compartment (known to be a subset of lyzosomes, therefore low pH vesicles) ( Fig. 3 & Supplementary Fig. 8 ). Our data in Figs.1 and Supplementary Fig. 7 suggest that anti-amyloidogenic activity of BACE2 is gene-dose dependent, and its level varies between individuals, with SNP allelic differences in BACE2 correlating with age of dementia onset. ./cache/cord-102481-obig3mu1.txt ./txt/cord-102481-obig3mu1.txt