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

David C. Hondius, Pim 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 journalArticleAcademicpeer-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 languageEnglish
Pages (from-to)654-668
JournalAlzheimers & Dementia
Volume12
Issue number6
DOIs
Publication statusPublished - Jun 2016

Cite this

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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 = "Disease, Extracellular Matrix, Hippocampus, Human, Immunoblotting, Immunohistochemistry, Mass Spectrometry, Proteins, Proteome, Proteomics, Research, biomarkers, methods, pathology, validation",
author = "Hondius, {David C.} and {van Nierop}, Pim 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 = "6",
doi = "10.1016/j.jalz.2015.11.002",
language = "English",
volume = "12",
pages = "654--668",
journal = "Alzheimers & Dementia",
issn = "1552-5260",
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Profiling the human hippocampal proteome at all pathologic stages of Alzheimer's disease. / Hondius, David C.; van Nierop, Pim; Li, Ka Wan; Hoozemans, Jeroen J. M.; van der Schors, Roel C.; van Haastert, Elise S.; van der Vies, Saskia M.; Rozemuller, Annemieke J. M.; Smit, August B.

In: Alzheimers & Dementia, Vol. 12, No. 6, 06.2016, p. 654-668.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

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

AU - Hondius, David C.

AU - van Nierop, Pim

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 - Disease

KW - Extracellular Matrix

KW - Hippocampus

KW - Human

KW - Immunoblotting

KW - Immunohistochemistry

KW - Mass Spectrometry

KW - Proteins

KW - Proteome

KW - Proteomics

KW - Research

KW - biomarkers

KW - methods

KW - pathology

KW - validation

U2 - 10.1016/j.jalz.2015.11.002

DO - 10.1016/j.jalz.2015.11.002

M3 - Article

VL - 12

SP - 654

EP - 668

JO - Alzheimers & Dementia

JF - Alzheimers & Dementia

SN - 1552-5260

IS - 6

ER -