Your browser doesn't support javascript.
loading
Disease and brain region specific immune response profiles in neurodegenerative diseases with pure and mixed protein pathologies.
Bathe, Tim; Hery, Gabriela P; Villareal, Jonathan A B; Phillips, Jennifer L; Cohen, Eric M; Sharma, Rohan V; Tsering, Wangchen; Prokop, Stefan.
Afiliación
  • Bathe T; Department of Pathology, Immunology & Laboratory Medicine, University of Florida, Gainesville, FL, 32610, USA.
  • Hery GP; Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL, 32610, USA.
  • Villareal JAB; McKnight Brain Institute, University of Florida, Gainesville, FL, 32610, USA.
  • Phillips JL; Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, 32608, USA.
  • Cohen EM; Department of Pathology, Immunology & Laboratory Medicine, University of Florida, Gainesville, FL, 32610, USA.
  • Sharma RV; Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL, 32610, USA.
  • Tsering W; Department of Pathology, Immunology & Laboratory Medicine, University of Florida, Gainesville, FL, 32610, USA.
  • Prokop S; Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL, 32610, USA.
Acta Neuropathol Commun ; 12(1): 54, 2024 Apr 05.
Article en En | MEDLINE | ID: mdl-38581050
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.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Neurodegenerativas / Enfermedad por Cuerpos de Lewy / Enfermedad de Alzheimer Límite: Animals / Humans Idioma: En Revista: Acta Neuropathol Commun Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Neurodegenerativas / Enfermedad por Cuerpos de Lewy / Enfermedad de Alzheimer Límite: Animals / Humans Idioma: En Revista: Acta Neuropathol Commun Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido