Preferential clustering of microglia and astrocytes around neuritic plaques during progression of Alzheimer's disease neuropathological changes DOI Creative Commons
Wangchen Tsering, Ana Cláudia Ferreira Rosa,

Isabelle Y. Ruan

и другие.

Journal of Neurochemistry, Год журнала: 2024, Номер 169(1)

Опубликована: Дек. 10, 2024

Neuroinflammation plays an important role in the pathological cascade of Alzheimer's disease (AD) along with aggregation extracellular amyloid-β (Aβ) plaques and intracellular aggregates tau protein. In animal models amyloidosis, local immune activation is centered around Aβ plaques, which are usually uniform morphology, dependent on transgenic model used. postmortem human brains a diversity plaque morphologies seen including diffuse (non-neuritic non-NP), dense-core cotton-wool NP. recent study, we demonstrated that during progression neuropathologic changes (ADNC), transformation non-NP into NP occurs tightly linked to emergence cortical, but not hippocampal neurofibrillary tangle (NFT) pathology. This highlights central AD pathogenesis as well brain region-specific differences formation. order correlate types activation, quantified clustering phenotype microglia accumulation astrocytes ADNC. We hypothesize glial response formation neuritic dystrophy First, show Iba1-positive preferentially cluster Utilizing phenotypic markers, furthermore demonstrate CD68-positive phagocytic strong preference both hippocampus frontal cortex. A similar preferential observed for CD11c ferritin-positive cortex, while this less pronounced hippocampus, highlighting between cortical plaques. Glial fibrillary acidic protein-positive showed clear cortex hippocampus. These data support notion intimately associated neuroimmune underscore importance interplay protein deposits system pathophysiology AD.

Язык: Английский

How the gut microbiota impacts neurodegenerative diseases by modulating CNS immune cells DOI Creative Commons
Philipp Schaible,

Julia Henschel,

Daniel Erny

и другие.

Journal of Neuroinflammation, Год журнала: 2025, Номер 22(1)

Опубликована: Март 3, 2025

Abstract Alzheimer’s disease (AD) is the most common neurodegenerative worldwide. Amyloid-β (Aβ) accumulation and neurofibrillary tangles are two key histological features resulting in progressive irreversible neuronal loss cognitive decline. The macrophages of central nervous system (CNS) belong to innate immune comprise parenchymal microglia CNS-associated (CAMs) at CNS interfaces (leptomeninges, perivascular space choroid plexus). Microglia CAMs have received attention as they may play a role onset progression e. g., by clearing amyloid beta through phagocytosis. Genome-wide association studies (GWAS) revealed that human express numerous risk genes for AD, further highlighting their potentially critical AD pathogenesis. tightly controlled environmental factors, such host microbiota. Notably, it was reported composition gut microbiota differed between patients healthy individuals. Hence, emerging analyzed impact bacteria different preclinical mouse models well clinical studies, enabling promising new therapeutic options.

Язык: Английский

Процитировано

1
Tau depletion diminishes vascular amyloid‐related deficits in a mouse model of cerebral amyloid angiopathy DOI Creative Commons
Nur Jury, Enrique Chimal‐Juárez, Henika Patel

и другие.

Alzheimer s & Dementia, Год журнала: 2025, Номер 21(5)

Опубликована: Май 1, 2025

Abstract INTRODUCTION Tau is essential for amyloid beta (Aβ)–induced synaptic and cognitive deficits in Alzheimer's disease (AD), making its downregulation a therapeutic target. Cerebral angiopathy (CAA), major vascular contributor to decline, affects over 90% of patients with AD. This study explores the impact tau on CAA pathogenesis. METHODS We crossed Familial Danish Dementia mouse model (Tg‐FDD), which develops amyloid, tau‐null (mTau −/− ) mice generate lacking endogenous (Tg‐FDD/mTau ). Behavioral, electrophysiological, histological, transcriptomic analyses were performed. RESULTS depletion ameliorated motor impairments, reduced deposition, prevented damage. ablation also mitigated astrocytic reactivity neuroinflammation associated accumulation. CONCLUSION These findings provide first vivo evidence beneficial effects model, supporting reduction as potential strategy parenchymal deposition. Highlights improves function impair, reduces cerebrovascular deposits, prevents damage cerebral (CAA). decreases reactivity, alters neuroinflammatory gene expression, enhances oligodendrocyte function, suggesting protective role against CAA. highlight mitigate CAA‐induced pathogenesis, implications treating both

Язык: Английский

Процитировано

0
Annexin A6 membrane repair protein protects against amyloid-induced dystrophic neurites and tau phosphorylation in Alzheimer’s disease model mice DOI Creative Commons

Katherine R. Sadleir,

Karen Gómez, A. Edwards

и другие.

Acta Neuropathologica, Год журнала: 2025, Номер 149(1)

Опубликована: Май 24, 2025

Язык: Английский

Процитировано

0
Down syndrome frontal cortex layer III and layer V pyramidal neurons exhibit lamina specific degeneration in aged individuals DOI Creative Commons
Melissa J. Alldred,

Kyrillos W. Ibrahim,

Harshitha Pidikiti

и другие.

Acta Neuropathologica Communications, Год журнала: 2024, Номер 12(1)

Опубликована: Ноя. 27, 2024

Abstract Selective vulnerability of neuronal populations occurs in both Down syndrome (DS) and Alzheimer’s disease (AD), resulting disproportional degeneration pyramidal neurons (PNs) affecting memory executive function. Elucidating the cellular mechanisms underlying selective these will provide pivotal insights for progression DS AD. Single population RNA-sequencing analysis was performed on critical function, prefrontal cortex Brodmann area 9 (BA9) layer III (L3) V (L5) excitatory PNs postmortem human age- sex-matched control (CTR) brains. Data mining differentially expressed genes (DEGs) from each lamina with DEGs divergent between identified interrogated. Bioinformatic inquiry L3 revealed more unique/differentially (uDEGs) than L5 compared to CTR subjects, indicating gene dysregulation shows spatial cortical laminar projection neuron dependent dysregulation. triplicated chromosome 21 (HSA21) comprised a subset only dysregulated or neurons, demonstrating partial specificity HSA21 expression. These uDEGs had disproportionally high number noncoding RNAs, suggesting specific dysfunctional regulation. overall pathways processes, many relevant early AD pathogenesis, while processes suggestive frank pathology. findings indicate that trisomy affects subpopulation BA9 aged individuals DS, which may inform circuit pathogenesis

Язык: Английский

Процитировано

1
Preferential clustering of microglia and astrocytes around neuritic plaques during progression of Alzheimer's disease neuropathological changes DOI Creative Commons
Wangchen Tsering, Ana Cláudia Ferreira Rosa,

Isabelle Y. Ruan

и другие.

Journal of Neurochemistry, Год журнала: 2024, Номер 169(1)

Опубликована: Дек. 10, 2024

Neuroinflammation plays an important role in the pathological cascade of Alzheimer's disease (AD) along with aggregation extracellular amyloid-β (Aβ) plaques and intracellular aggregates tau protein. In animal models amyloidosis, local immune activation is centered around Aβ plaques, which are usually uniform morphology, dependent on transgenic model used. postmortem human brains a diversity plaque morphologies seen including diffuse (non-neuritic non-NP), dense-core cotton-wool NP. recent study, we demonstrated that during progression neuropathologic changes (ADNC), transformation non-NP into NP occurs tightly linked to emergence cortical, but not hippocampal neurofibrillary tangle (NFT) pathology. This highlights central AD pathogenesis as well brain region-specific differences formation. order correlate types activation, quantified clustering phenotype microglia accumulation astrocytes ADNC. We hypothesize glial response formation neuritic dystrophy First, show Iba1-positive preferentially cluster Utilizing phenotypic markers, furthermore demonstrate CD68-positive phagocytic strong preference both hippocampus frontal cortex. A similar preferential observed for CD11c ferritin-positive cortex, while this less pronounced hippocampus, highlighting between cortical plaques. Glial fibrillary acidic protein-positive showed clear cortex hippocampus. These data support notion intimately associated neuroimmune underscore importance interplay protein deposits system pathophysiology AD.

Язык: Английский

Процитировано

1