Regional protein expression in human Alzheimer's brain correlates with disease severity

Jingshu Xu; Stefano Patassini; Nitin Rustogi; Isabel Riba Garcia; Benjamin D Hale; Alexander M. Phillips; Henry J Waldvogel; Robert Haines; Philip Bradbury; Frederick Stevens; Richard L. M.  Faull; Andrew Dowsey; Garth JS Cooper; Richard Unwin

doi:10.1038/s42003-018-0254-9

Regional protein expression in human Alzheimer's brain correlates with disease severity

Jingshu Xu, Stefano Patassini, Nitin Rustogi, Isabel Riba Garcia, Benjamin D Hale, Alexander M. Phillips, Henry J Waldvogel, Robert Haines, Philip Bradbury, Frederick Stevens, Richard L. M. Faull, Andrew Dowsey, Garth JS Cooper, Richard Unwin

University of Auckland

Research output: Contribution to journal › Article › peer-review

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that currently affects 36 million people worldwide with no effective treatment available. Development of AD follows a distinctive pattern in the brain and is poorly modelled in animals. Therefore, it is vital to widen both the spatial scope of the study of AD and prioritise the study of human brains. Here we show that functionally distinct human brain regions show varying and region-specific changes in protein expression. These changes provide novel insights into the progression of disease, novel AD-related pathways, the presence of a gradient of protein expression change from less to more affected regions, and the presence of a protective protein expression profile in the cerebellum. This spatial proteomics analysis provides a framework which can underpin current research and opens new avenues of interest to enhance our understanding of molecular pathophysiology of AD, provides new targets for intervention and broadens the conceptual frameworks for future AD research.

Original language	English
Journal	Communications Biology
Early online date	4 Feb 2019
DOIs	https://doi.org/10.1038/s42003-018-0254-9
Publication status	Published - 2019

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title = "Regional protein expression in human Alzheimer's brain correlates with disease severity",

abstract = "Alzheimer's disease (AD) is a progressive neurodegenerative disorder that currently affects 36 million people worldwide with no effective treatment available. Development of AD follows a distinctive pattern in the brain and is poorly modelled in animals. Therefore, it is vital to widen both the spatial scope of the study of AD and prioritise the study of human brains. Here we show that functionally distinct human brain regions show varying and region-specific changes in protein expression. These changes provide novel insights into the progression of disease, novel AD-related pathways, the presence of a gradient of protein expression change from less to more affected regions, and the presence of a protective protein expression profile in the cerebellum. This spatial proteomics analysis provides a framework which can underpin current research and opens new avenues of interest to enhance our understanding of molecular pathophysiology of AD, provides new targets for intervention and broadens the conceptual frameworks for future AD research.",

author = "Jingshu Xu and Stefano Patassini and Nitin Rustogi and {Riba Garcia}, Isabel and Hale, {Benjamin D} and Phillips, {Alexander M.} and Waldvogel, {Henry J} and Robert Haines and Philip Bradbury and Frederick Stevens and Faull, {Richard L. M.} and Andrew Dowsey and Cooper, {Garth JS} and Richard Unwin",

year = "2019",

doi = "10.1038/s42003-018-0254-9",

language = "English",

journal = "Communications Biology",

issn = "2399-3642",

publisher = "Springer Nature",

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TY - JOUR

T1 - Regional protein expression in human Alzheimer's brain correlates with disease severity

AU - Xu, Jingshu

AU - Patassini, Stefano

AU - Rustogi, Nitin

AU - Riba Garcia, Isabel

AU - Hale, Benjamin D

AU - Phillips, Alexander M.

AU - Waldvogel, Henry J

AU - Haines, Robert

AU - Bradbury, Philip

AU - Stevens, Frederick

AU - Faull, Richard L. M.

AU - Dowsey, Andrew

AU - Cooper, Garth JS

AU - Unwin, Richard

PY - 2019

Y1 - 2019

N2 - Alzheimer's disease (AD) is a progressive neurodegenerative disorder that currently affects 36 million people worldwide with no effective treatment available. Development of AD follows a distinctive pattern in the brain and is poorly modelled in animals. Therefore, it is vital to widen both the spatial scope of the study of AD and prioritise the study of human brains. Here we show that functionally distinct human brain regions show varying and region-specific changes in protein expression. These changes provide novel insights into the progression of disease, novel AD-related pathways, the presence of a gradient of protein expression change from less to more affected regions, and the presence of a protective protein expression profile in the cerebellum. This spatial proteomics analysis provides a framework which can underpin current research and opens new avenues of interest to enhance our understanding of molecular pathophysiology of AD, provides new targets for intervention and broadens the conceptual frameworks for future AD research.

AB - Alzheimer's disease (AD) is a progressive neurodegenerative disorder that currently affects 36 million people worldwide with no effective treatment available. Development of AD follows a distinctive pattern in the brain and is poorly modelled in animals. Therefore, it is vital to widen both the spatial scope of the study of AD and prioritise the study of human brains. Here we show that functionally distinct human brain regions show varying and region-specific changes in protein expression. These changes provide novel insights into the progression of disease, novel AD-related pathways, the presence of a gradient of protein expression change from less to more affected regions, and the presence of a protective protein expression profile in the cerebellum. This spatial proteomics analysis provides a framework which can underpin current research and opens new avenues of interest to enhance our understanding of molecular pathophysiology of AD, provides new targets for intervention and broadens the conceptual frameworks for future AD research.

U2 - 10.1038/s42003-018-0254-9

DO - 10.1038/s42003-018-0254-9

M3 - Article

JO - Communications Biology

JF - Communications Biology

SN - 2399-3642

ER -

Regional protein expression in human Alzheimer's brain correlates with disease severity

Abstract

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