The proteome of the dentate terminal zone of the perforant path indicates presynaptic impairment in Alzheimer disease.

The proteome of the dentate terminal zone of the perforant path indicates presynaptic impairment in Alzheimer disease. Mol Cell Proteomics. 2019 Nov 07;: Authors: Haytural H, Mermelekas G, Emre C, Nigam SM, Carroll SL, Winblad B, Bogdanovic N, Barthet G, Granholm AC, Orre LM, Tjernberg LO, Frykman S Abstract Synaptic dysfunction is an early pathogenic event in Alzheimer disease (AD) that contributes to network disturbances and cognitive decline. Some synapses are more vulnerable than others, including the synapses of the perforant path, which provides the main excitatory input to the hippocampus. To elucidate the molecular mechanisms underlying the dysfunction of these synapses, we performed an explorative proteomic study of the dentate terminal zone of the perforant path. The outer two-thirds of the molecular layer of the dentate gyrus, where the perforant path synapses are located, was microdissected from five subjects with AD and five controls. The microdissected tissues were dissolved and digested by trypsin. Peptides from each sample were labelled with different isobaric tags, pooled together and pre-fractionated into 72 fractions by high-resolution isoelectric focusing. Each fraction was then analyzed by liquid chromatography-mass spectrometry. We quantified the relative expression levels of 7322 proteins, whereof 724 showed significantly altered levels in AD. Our comprehensive data analysis using enrichment and pathway analyse...
Source: Molecular and Cellular Proteomics : MCP - Category: Molecular Biology Authors: Tags: Mol Cell Proteomics Source Type: research