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Enhanced microglial dynamics and a paucity of tau seeding in the amyloid plaque microenvironment contribute to cognitive resilience in Alzheimer's disease.
Jury-Garfe, Nur; Redding-Ochoa, Javier; You, Yanwen; Martínez, Pablo; Karahan, Hande; Chimal-Juárez, Enrique; Johnson, Travis S; Zhang, Jie; Resnick, Susan; Kim, Jungsu; Troncoso, Juan C; Lasagna-Reeves, Cristian A.
Afiliação
  • Jury-Garfe N; Stark Neurosciences Research Institute, Indiana University School of Medicine, Neurosciences Research Building 214G, 320 West 15th Street, Indianapolis, IN, 46202, USA.
  • Redding-Ochoa J; Department of Anatomy, Cell Biology and Physiology, Indiana University School of Medicine, Indianapolis, IN, USA.
  • You Y; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, USA.
  • Martínez P; Stark Neurosciences Research Institute, Indiana University School of Medicine, Neurosciences Research Building 214G, 320 West 15th Street, Indianapolis, IN, 46202, USA.
  • Karahan H; Department of Anatomy, Cell Biology and Physiology, Indiana University School of Medicine, Indianapolis, IN, USA.
  • Chimal-Juárez E; Stark Neurosciences Research Institute, Indiana University School of Medicine, Neurosciences Research Building 214G, 320 West 15th Street, Indianapolis, IN, 46202, USA.
  • Johnson TS; Department of Anatomy, Cell Biology and Physiology, Indiana University School of Medicine, Indianapolis, IN, USA.
  • Zhang J; Stark Neurosciences Research Institute, Indiana University School of Medicine, Neurosciences Research Building 214G, 320 West 15th Street, Indianapolis, IN, 46202, USA.
  • Resnick S; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, USA.
  • Kim J; Stark Neurosciences Research Institute, Indiana University School of Medicine, Neurosciences Research Building 214G, 320 West 15th Street, Indianapolis, IN, 46202, USA.
  • Troncoso JC; Department of Anatomy, Cell Biology and Physiology, Indiana University School of Medicine, Indianapolis, IN, USA.
  • Lasagna-Reeves CA; Department of Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, USA.
Acta Neuropathol ; 148(1): 15, 2024 Aug 05.
Article em En | MEDLINE | ID: mdl-39102080
ABSTRACT
Asymptomatic Alzheimer's disease (AsymAD) describes the status of individuals with preserved cognition but identifiable Alzheimer's disease (AD) brain pathology (i.e., beta-amyloid (Aß) deposits, neuritic plaques, and neurofibrillary tangles) at autopsy. In this study, we investigated the postmortem brains of a cohort of AsymAD subjects to gain insight into the mechanisms underlying resilience to AD pathology and cognitive decline. Our results showed that AsymAD cases exhibit enrichment in core plaques, decreased filamentous plaque accumulation, and increased plaque-surrounding microglia. Less pathological tau aggregation in dystrophic neurites was found in AsymAD brains than in AD brains, and tau seeding activity was comparable to that in healthy brains. We used spatial transcriptomics to characterize the plaque niche further and revealed autophagy, endocytosis, and phagocytosis as the pathways associated with the genes upregulated in the AsymAD plaque niche. Furthermore, the levels of ARP2 and CAP1, which are actin-based motility proteins that participate in the dynamics of actin filaments to allow cell motility, were increased in the microglia surrounding amyloid plaques in AsymAD cases. Our findings suggest that the amyloid-plaque microenvironment in AsymAD cases is characterized by the presence of microglia with highly efficient actin-based cell motility mechanisms and decreased tau seeding compared with that in AD brains. These two mechanisms can potentially protect against the toxic cascade initiated by Aß, preserving brain health, and slowing AD pathology progression.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas tau / Microglia / Placa Amiloide / Doença de Alzheimer Limite: Aged / Aged80 / Female / Humans / Male Idioma: En Revista: Acta Neuropathol Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas tau / Microglia / Placa Amiloide / Doença de Alzheimer Limite: Aged / Aged80 / Female / Humans / Male Idioma: En Revista: Acta Neuropathol Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos