ArticleActa neuropathologica communications2024
Disease and brain region specific immune response profiles in neurodegenerative diseases with pure and mixed protein pathologies.
Article in Acta neuropathologica communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 10 citations in OpenAlex.
- A pattern to rule them all: tracing a human brain map of molecular aspects shared by Alzheimer's disease and dementia with Lewy bodies.GeroScience · 2026Article
- Corpora amylacea profiling reveals disease stage and brain region-specific alterations in glycogen metabolism in Alzheimer's disease patient brains.Cell reports. Medicine · 2026Article
- Simultaneous spatial transcriptomics and morphology profiling as tools to explore how microglia change with age.Nature aging · 2026Article
- Early Amyloid Formation and Neuroinflammatory Response in a Bigenic Mouse Model Expressing Human α-Synuclein and Aβ.Parkinson's disease · 2026Article
- Spilling the T: T cells in tauopathy mechanisms, disease progression, and therapeutic horizons.Molecular neurodegeneration advances · 2026Review
- A Spatially Resolved View on the Aging Substantia nigra: An Exploratory Proteomic Study.Advanced biology · 2025Article
- Brain Region-Specific Accumulation of Amyloidosis-Associated Proteins in Postmortem Brain Tissues of Alzheimer's Disease Patients.Molecular neurobiology · 2025Article
- Combined neocortical protein and morphological profiling of reactive microglia across Alzheimer's and Creutzfeldt-Jakob disease.Acta neuropathologica communications · 2025Article
- Digital neuropathology of neurodegenerative disorders: Foundations, research advances, and future directions.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Preferential clustering of microglia and astrocytes around neuritic plaques during progression of Alzheimer's disease neuropathological changes.Journal of neurochemistry · 2025Article
- The dual role of microglia in Alzheimer's disease: from immune regulation to pathological progression.Frontiers in aging neuroscience · 2025Review
- Deterioration of neuroimmune homeostasis in Alzheimer's Disease patients who survive a COVID-19 infection.Journal of neuroinflammation · 2024Article
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8 authors at 1 institution in 1 country.
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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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