Decreased drebrin mRNA expression in Alzheimer disease: correlation with tau pathology.
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 Abeta(40) (+464%; P < 0.05), Abeta(42) (+369%; P < 0.0001), Abeta(42/40) 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 (r(2) = +0.244) but negatively with duration of symptoms (r(2) = -0.357) and PHFtau (r(2) = -0.248). Drebrin mRNA levels were correlated to a lesser degree with the drebrin protein content (r(2) = +0.136) and with sim2 (r(2) = +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.
Julien
Carl
C
Molecular Endocrinology and Oncology Research Center, Centre Hospitalier de l'Universitè, Laval Research Center, Quebec, Quebec, Canada.
Tremblay
Cyntia
C
Bendjelloul
Farid
F
Phivilay
Alix
A
Coulombe
Marie-Andrée
MA
Emond
Vincent
V
Calon
Frédéric
F
D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D009479:Neuropeptides / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis*; D016875:tau Proteins / Q000378:metabolism*
D009479:Neuropeptides; D012333:RNA, Messenger; C053386:drebrins; D016875:tau Proteins