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Profiling the human hippocampal proteome at all pathologic stages of Alzheimer's disease
Author(s) -
Hondius David C.,
Nierop Pim,
Li Ka Wan,
Hoozemans Jeroen J.M.,
Schors Roel C.,
Haastert Elise S.,
Vies Saskia M.,
Rozemuller Annemieke J.M.,
Smit August B.
Publication year - 2016
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.2015.11.002
Subject(s) - laser capture microdissection , subiculum , proteomics , hippocampal formation , proteome , biology , hippocampus , quantitative proteomics , alzheimer's disease , neuroscience , pathology , disease , bioinformatics , dentate gyrus , medicine , gene expression , biochemistry , gene
We performed a comprehensive quantitative proteomics study on human hippocampus tissue involving all Braak stages to assess changes in protein abundance over the various stages of Alzheimer's disease (AD). Methods Hippocampal subareas CA1 and subiculum of 40 cases were isolated using laser capture microdissection and analyzed using mass spectrometry. Immunoblotting and immunohistochemistry were used for validation. Results Over the Braak stages, an altered expression was found for 372 proteins including changes in levels of extracellular matrix components, and in calcium‐dependent signaling proteins. Early changes were observed in levels of proteins related to cytoskeletal dynamics and synaptic components including an increase in RIMS1 and GRIK4. Several synaptic proteins, such as BSN, LIN7A, DLG2, ‐3, and ‐4, exhibit an early‐up, late‐down expression pattern. Discussion This study provides new insight into AD‐dependent changes in protein levels in the hippocampus during AD pathology, identifying potential novel therapeutic targets and biomarkers.