Takashi Saito 2, Takaomi Saido2, Masaaki Hokama1, 9, Toru Iwaki 3, Tomoyuki Ohara4, Toshiharu Ninomiya5, Yutaka Kiyohara6, Kunihiko Sakumi1, Frank M. LaFerla7 & Yusaku Nakabeppu

摘要: Results Altered gene expression profiles in cortices of AD patients and AD mouse models. Previously, we obtained gene expression profiles from three human brain regions––hippocampus and the temporal and frontal cortices––prepared from post-mortem brains of AD subjects, and found a significant alteration in the hippocampal gene expression profile with AD pathologies 18. In the present study, we aimed to characterise gene expression profiles in AD cortical regions by re-analysing the microarray data from temporal and frontal cortices of AD patients and controls (Supplementary Tables S1 and S2), using the Affymetrix Expression Console and Transcriptome Analysis Console (TAC) software.As shown in Fig. 1a and b, the temporal (8 AD and 10 non-AD cases) and frontal (13 AD and 17 non-AD cases) samples with no overlapped distribution in the Principal Component Analysis (PCA) exhibited clear separation of AD and non-AD cases by hierarchical clustering of their expression profiles (Supplementary Figs S1 and S2). By analysing expression profiles of these subjects using TAC and Ingenuity Pathway Analysis (IPA) software, we found that 1372 (781 up, 591 down) genes in the temporal cortex and 236 (33 up, 203 down) genes in the frontal cortex were differentially expressed between AD and non-AD cases (ANOVA: P< 0.05, a lower bi-weight average signal (log2)> 6.64, a fold change≥ 1.2 or≤− 1.2)(Supplementary Tables S3 and S4). We then validated the microarray data of 10 transcripts by real-time quantitative RT-PCR (qRT-PCR) analyses (primers shown in Supplementary Table S5) in six AD (3 males and 3 females) and six …