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

Abstract

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.

Drebrin A expression is altered after pilocarpine‐induced seizures: Time course of changes is consistent for a role in the integrity and stability of dendritic spines of hippocampal granule cells

“…1A) and the granule cells of the DG (Figs. 1A,B), as previously reported in human brain (Julien et al, 2008). In addition, many nonprincipal cells were also labeled for DA mRNA (Fig.…”

Accumulation of amyloid-β in the cerebellar cortex of essential tremor patients

“…The fact that levels of phosphorylated tau at epitope S396 and S404 were higher in the cerebellum of ET subgroup with high cerebellar Aβ42 and correlated with insoluble Aβ42 concentrations are in accordance with an extended AD-like neuropathology in the cerebellum of this subset of ET subjects and suggests that this particular subset was not simply preclinical AD. Moreover, the significant higher levels of insoluble Aβ42 were not associated with higher levels of insoluble phosphorylated tau in the parietal cortex of ET and remained clearly lower that what is found in advanced AD (Tremblay et al 2007;Julien et al 2008). …”

“…Table 1 shows a summary of the relevant information available regarding the subjects involved in the study (9 ET, 10 PD and 16 Controls). Additional information on the subjects has been detailed elsewhere for both ET/PD (Rajput et al 2011;Paris-Robidas et al 2012;Delay et al 2014) and AD (Julien et al 2008;Julien et al 2009) series.…”

“…Aβ42 are both increased in brain samples from AD compared to non-demented Controls (Lue et al 1999;McLean et al 1999;Wang et al 1999;Näslund et al 2000;Fonte et al 2001;Ingelsson et al 2004;Forman et al 2007;Tremblay et al 2007;Julien et al 2008). By applying a procedure that extracts insoluble proteins from brain samples using sequentially buffered water, detergent and formic acid (FA), Aβ peptides are segregated into biochemical compartments defined by their solubility (Tremblay et al 2007;Steinerman et al 2008).…”

“…The other half was immediately frozen at -80°C and later cut by hand in the frontal plane into 2-3 mm thick slices. For homogenate-based studies such as Western immunoblotting or ELISA, cerebellar cortex extracts (~100 mg) were homogenized and processed to generate a tris-buffered saline (TBS)-soluble fraction containing extracellular and cytosolic proteins, a detergent-soluble fraction containing membrane-bound proteins and a formic-acid-soluble fraction containing detergent-insoluble proteins, as described in detail previously (Tremblay et al 2007;Julien et al 2008 Triton X-100, 0.5% SDS, and 0.5% deoxycholate) containing the same protease and phosphatase inhibitors. The resulting homogenate was centrifuged at 100 000 × g for 20 min at 4°C to produce the detergent-soluble protein fraction.…”