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P4‐374: Neuropsychological differences between PiB‐negative subcortical vascular dementia and PiB‐positive Alzheimer's disease
Author(s) -
Yoon Cindy
Publication year - 2012
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2013.08.155
Subject(s) - neuropsychology , medicine , neuropsychological test , dementia , post hoc analysis , vascular dementia , psychology , disease , psychiatry , cognition
TrkB-Shc) following cellular exposure to amyloid beta 1-42 (Ab42) oligomers and fibrils (all p<0.045). As this suggested dysregulation in TrkB premRNA splicing in AD, we conducted an in silico screening for putative splice regulatory protein binding sites in the intron/exon splice regulatory regions of exons 18 and 19 of the TrkB gene. From the candidate splice regulatory proteins identified, we assessed their gene expression profiles using a microarray database of control/AD postmortem human hippocampal brain tissue. We found significant alterations in Srp20 gene expression in AD cases. When we assessed Srp20 gene expression in our postmortem brain cohort of control andAD (n1⁄46/6), we found elevated Srp20mRNA levels in theADhippocampus (t1⁄43.44, df1⁄48, p1⁄40.009). Furthermore, Srp20 mRNA levels were significantly increased in SHSY5Y cells treated with Ab42 fibrils (t1⁄43.84, df1⁄415, p1⁄40.002). When Srp20 was overexpressed, we found increased exon 19 inclusion in TrkB minigene transcripts and corresponding increases in endogenous TrkB-Shc mRNA levels (t1⁄43.76, df1⁄44, p1⁄40.04). Conversely, when we knocked down Srp20 expression, we observed the opposite effect on TrkBShc expression (t1⁄4-3.50, df1⁄46, p1⁄40.01). Conclusions: We identify a novel mechanism by which BDNF signaling is compromised in AD. Our findings suggest that dysregulation of factors regulating pre-mRNA splicing may underlie gene expression changes that occur in AD.