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Open Access 01-12-2024 | Alzheimer's Disease | Research

Disease and brain region specific immune response profiles in neurodegenerative diseases with pure and mixed protein pathologies

Authors: Tim Bathe, Gabriela P. Hery, Jonathan A. B. Villareal, Jennifer L. Phillips, Eric M. Cohen, Rohan V. Sharma, Wangchen Tsering, Stefan Prokop

Published in: Acta Neuropathologica Communications | Issue 1/2024

Abstract

The disease-specific accumulation of pathological proteins has long been the major focus of research in neurodegenerative diseases (ND), including Alzheimer’s disease (AD) and related dementias (RD), but the recent identification of a multitude of genetic risk factors for ND in immune-associated genes highlights the importance of immune processes in disease pathogenesis and progression. Studies in animal models have characterized the local immune response to disease-specific proteins in AD and ADRD, but due to the complexity of disease processes and the co-existence of multiple protein pathologies in human donor brains, the precise role of immune processes in ND is far from understood. To better characterize the interplay between different extracellular and intracellular protein pathologies and the brain’s intrinsic immune system in ND, we set out to comprehensively profile the local immune response in postmortem brain samples of individuals with “pure” beta-Amyloid and tau pathology (AD), “pure” α-Synuclein pathology in Lewy body diseases (LBD), as well as cases with Alzheimer’s disease neuropathological changes (ADNC) and Lewy body pathology (MIX). Combining immunohistochemical profiling of microglia and digital image analysis, along with deep immunophenotyping using gene expression profiling on the NanoString nCounter® platform and digital spatial profiling on the NanoString GeoMx® platform we identified a robust immune activation signature in AD brain samples. This signature is maintained in persons with mixed pathologies, irrespective of co-existence of AD pathology and Lewy body (LB) pathology, while LBD brain samples with “pure” LB pathology exhibit an attenuated and distinct immune signature. Our studies highlight disease- and brain region-specific immune response profiles to intracellular and extracellular protein pathologies and further underscore the complexity of neuroimmune interactions in ND.

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Title: Disease and brain region specific immune response profiles in neurodegenerative diseases with pure and mixed protein pathologies
Authors: Tim Bathe
Gabriela P. Hery
Jonathan A. B. Villareal
Jennifer L. Phillips
Eric M. Cohen
Rohan V. Sharma
Wangchen Tsering
Stefan Prokop
Publication date: 01-12-2024
Publisher: BioMed Central
Keywords: Alzheimer's Disease
Alzheimer's Disease
Pathology
Published in: Acta Neuropathologica Communications / Issue 1/2024
Electronic ISSN: 2051-5960
DOI: https://doi.org/10.1186/s40478-024-01770-7

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Disease and brain region specific immune response profiles in neurodegenerative diseases with pure and mixed protein pathologies

Abstract

Keynote webinar | Spotlight on medication adherence

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Abstract

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