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

D. Hondius; P. van Nierop; Ka Wan Li; Jeroen J M Hoozemans; Roel C van der Schors; Elise S van Haastert; Saskia M van der Vies; Annemieke J M Rozemuller; August B Smit

doi:10.1016/j.jalz.2015.11.002

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

D. Hondius, P. van Nierop, Ka Wan Li, Jeroen J M Hoozemans, Roel C van der Schors, Elise S van Haastert, Saskia M van der Vies, Annemieke J M Rozemuller, August B Smit

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

INTRODUCTION: 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.

Original language	English
Pages (from-to)	654-68
Number of pages	15
Journal	Alzheimers & Dementia
Volume	12
Issue number	6
DOIs	https://doi.org/10.1016/j.jalz.2015.11.002
Publication status	Published - Jun 2016

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Journal Article

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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@article{727d823f7d7a46138136c669600da9e3,

title = "Profiling the human hippocampal proteome at all pathologic stages of Alzheimer's disease",

abstract = "INTRODUCTION: 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.",

keywords = "Journal Article",

author = "D. Hondius and {van Nierop}, P. and Li, {Ka Wan} and Hoozemans, {Jeroen J M} and {van der Schors}, {Roel C} and {van Haastert}, {Elise S} and {van der Vies}, {Saskia M} and Rozemuller, {Annemieke J M} and Smit, {August B}",

year = "2016",

month = jun,

doi = "10.1016/j.jalz.2015.11.002",

language = "English",

volume = "12",

pages = "654--68",

journal = "Alzheimers & Dementia",

issn = "1552-5260",

publisher = "Elsevier Inc.",

number = "6",

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TY - JOUR

T1 - Profiling the human hippocampal proteome at all pathologic stages of Alzheimer's disease

AU - Hondius, D.

AU - van Nierop, P.

AU - Li, Ka Wan

AU - Hoozemans, Jeroen J M

AU - van der Schors, Roel C

AU - van Haastert, Elise S

AU - van der Vies, Saskia M

AU - Rozemuller, Annemieke J M

AU - Smit, August B

PY - 2016/6

Y1 - 2016/6

N2 - INTRODUCTION: 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.

AB - INTRODUCTION: 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.

KW - Journal Article

U2 - 10.1016/j.jalz.2015.11.002

DO - 10.1016/j.jalz.2015.11.002

M3 - Article

C2 - 26772638

SN - 1552-5260

VL - 12

SP - 654

EP - 668

JO - Alzheimers & Dementia

JF - Alzheimers & Dementia

IS - 6

ER -