Decreased drebrin mRNA expression in Alzheimer disease: Correlation with tau pathology

• Published in: Journal of neuroscience research 2008-08, Vol.86 (10), p.2292-2302
• Main Authors: Julien, Carl, Tremblay, Cyntia, Bendjelloul, Farid, Phivilay, Alix, Coulombe, Marie-Andrée, Émond, Vincent, Calon, Frédéric
• Format: Article
• Language: English
• Subjects: Aged; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Blotting, Western; Brain - metabolism; Brain - pathology; Down-Regulation; drebrin; Female; Humans; In Situ Hybridization; Male; Neuropeptides - biosynthesis; RNA, Messenger - biosynthesis; sim2; tau; tau Proteins - metabolism; β-amyloid peptide
• ISSN: 0360-4012; 1097-4547
• DOI: 10.1002/jnr.21667

To investigate the mRNA expression of the dendritic spine protein drebrin in Alzheimer's disease (AD), we performed post‐mortem in situ hybridization studies in brain sections from 20 AD patients and 21 controls. AD diagnosis was confirmed by decreased drebrin protein and increased Aβ40 (+464%; P < 0.05), Aβ42 (+369%; P < 0.0001), Aβ42/40 ratio (+226%; P < 0.01), total tau (+2,725%; P < 0.0001), and paired helical filament tau (PHFtau; +867%; P < 0.001) compared with controls. We found significant decreases in drebrin mRNA in the parietal cortex (–27%; P < 0.01), the temporal cortex (–22%; P < 0.05), and the hippocampus (–25%; P < 0.05) of AD patients compared with controls. Cortical levels of drebrin mRNA correlated positively with soluble total tau (r2 = +0.244) but negatively with duration of symptoms (r2 = −0.357) and PHFtau (r2 = −0.248). Drebrin mRNA levels were correlated to a lesser degree with the drebrin protein content (r2 = +0.136) and with sim2 (r2 = +0.176), a potential modulator of drebrin transcription. Our results suggest that the down‐regulation of drebrin mRNA expression plays an important role in AD and is closely related to the progression of the disease. © 2008 Wiley‐Liss, Inc.