Fig 1: Exacerbated α-synuclein accumulation in apoE4 cerebral organoids and postmortem brains from APOE4 carriers. Cerebral organoids were generated from iPSC lines carrying APOE ε3/ε3 (APOE3/3) or ε4/ε4 (APOE4/4) genotype and subjected to analyses at Day 90. a–d, Amounts of αSyn (b), p-αSyn (c) and apoE (d) in the RIPA fraction of the iPSC-derived cerebral organoids were quantified by Western blotting. e–j, Amounts of αSyn (f), p-αSyn (g) and apoE (h) in the SDS fraction of the iPSC-derived cerebral organoids were quantified by Western blotting. ApoE, αSyn, and p-αSyn levels were normalized to β-actin levels. Spearman correlation analyses for apoE vs. αSyn (i) and apoE vs. p-αSyn (j) in SDS fraction are shown with the correlation coefficient (r) and the correlation p value. Experiments were repeated in two independent differentiation batches. Lysates of 3 cerebral organoids from each line were analyzed as one sample. All data are expressed as mean ± SEM (N = 5 lines/each). k–l, Postmortem brain sections from the superior temporal cortex of Lowy body dementia (LBD) subjects with or without APOE4 were immunostained with apoE antibody and anti-αSyn NACP98 antibody for Lewy body. Representative images for the deposition of apoE in NACP-positive Lewy bodies are shown (k). Scale bar: 20 µm. The colocalization of apoE with NACP-positive Lewy bodies was quantified by Image J (l). All data are expressed as mean ± SEM (N = 17 patients/each). Mann–Whitney U tests were performed to determine statistical significance. *p < 0.05, **p < 0.01, ***p < 0.001