Profiling the human hippocampal proteome at all pathologic stages of Alzheimer's disease

Alzheimer's & Dementia - Tập 12 - Trang 654-668 - 2016
David C. Hondius1,2, Pim van Nierop2, Ka Wan Li2, Jeroen J.M. Hoozemans1, Roel C. van der Schors2, Elise S. van Haastert1, Saskia M. van der Vies1, Annemieke J.M. Rozemuller1, August B. Smit2
1Department of Pathology, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, The Netherlands
2Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University Amsterdam, Amsterdam, The Netherlands

Tóm tắt

AbstractIntroductionWe 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).MethodsHippocampal 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.ResultsOver 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.DiscussionThis study provides new insight into AD‐dependent changes in protein levels in the hippocampus during AD pathology, identifying potential novel therapeutic targets and biomarkers.

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Alzheimer's & Dementia

Tập 12

654-668

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