ArticleBrain pathology (Zurich, Switzerland)2021
Accumulation of neurofibrillary tangles and activated microglia is associated with lower neuron densities in the aphasic variant of Alzheimer's disease.
Article in Brain pathology (Zurich, Switzerland), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 57 citations in OpenAlex.
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- Combined impact of neutrophil-to-high-density lipoprotein cholesterol ratio (NHR) and cognitive function on all-cause mortality in older adults: a population-based study.Lipids in health and disease · 2025Article
- Inspecting the Triazole Scaffold as Powerful Antifibril Agents against 2N4R Tau and α-Synuclein Aggregates.ACS omega · 2025Article
- An overview on microglial origin, distribution, and phenotype in Alzheimer's disease.Journal of cellular physiology · 2024Review
- Automated deep learning segmentation of high-resolution 7 Tesla postmortem MRI for quantitative analysis of structure-pathology correlations in neurodegenerative diseases.Imaging neuroscience (Cambridge, Mass.) · 2024Article
- Microglia in brain aging: An overview of recent basic science and clinical research developments.Journal of biomedical research · 2024Article
- Evaluation of specific binding of [American journal of nuclear medicine and molecular imaging · 2024Article
- Reevaluating tau reduction as a therapeutic approach for tauopathies: Insights and perspectives.Cytoskeleton (Hoboken, N.J.) · 2024Article
- A computational model of Alzheimer's disease at the nano, micro, and macroscales.Frontiers in neuroinformatics · 2024Article
- Atypical intrinsic neural timescale in the left angular gyrus in Alzheimer's disease.Brain communications · 2024Article
- Tau Oligomer-Containing Synapse Elimination by Microglia and Astrocytes in Alzheimer Disease.JAMA neurology · 2023Article
- Palmitoylethanolamide shows limited efficacy in controlling cerebral cryptococcosisAntimicrobial agents and chemotherapy · 2023Article
- Ependyma in Neurodegenerative Diseases, Radiation-Induced Brain Injury and as a Therapeutic Target for Neurotrophic Factors.Biomolecules · 2023Review
- Phospholipase B Is Critical for Cryptococcus neoformans Survival in the Central Nervous System.mBio · 2023Article
- Palmitoylethanolamide shows limited efficacy in controlling cerebral cryptococcosisbioRxiv : the preprint server for biology · 2023Article
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Authors and funding
11 authors at 1 institution in 1 country.
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Abstract
The neurofibrillary tangles (NFT) and amyloid-ß plaques (AP) that comprise Alzheimer's disease (AD) neuropathology are associated with neurodegeneration and microglial activation. Activated microglia exist on a dynamic spectrum of morphologic subtypes that include resting, surveillant microglia capable of converting to activated, hypertrophic microglia closely linked to neuroinflammatory processes and AD neuropathology in amnestic AD. However, quantitative analyses of microglial subtypes and neurons are lacking in non-amnestic clinical AD variants, including primary progressive aphasia (PPA-AD). PPA-AD is a language disorder characterized by cortical atrophy and NFT densities concentrated to the language-dominant hemisphere. Here, a stereologic investigation of five PPA-AD participants determined the densities and distributions of neurons and microglial subtypes to examine how cellular changes relate to AD neuropathology and may contribute to cortical atrophy. Adjacent series of sections were immunostained for neurons (NeuN) and microglia (HLA-DR) from bilateral language and non-language regions where in vivo cortical atrophy and Thioflavin-S-positive APs and NFTs were previously quantified. NeuN-positive neurons and morphologic subtypes of HLA-DR-positive microglia (i.e., resting [ramified] microglia and activated [hypertrophic] microglia) were quantified using unbiased stereology. Relationships between neurons, microglia, AD neuropathology, and cortical atrophy were determined using linear mixed models. NFT densities were positively associated with hypertrophic microglia densities (P < 0.01) and inversely related to neuron densities (P = 0.01). Hypertrophic microglia densities were inversely related to densities of neurons (P < 0.01) and ramified microglia (P < 0.01). Ramified microglia densities were positively associated with neuron densities (P = 0.02) and inversely related to cortical atrophy (P = 0.03). Our findings provide converging evidence of divergent roles for microglial subtypes in patterns of neurodegeneration, which includes hypertrophic microglia likely driving a neuroinflammatory response more sensitive to NFTs than APs in PPA-AD. Moreover, the accumulation of both NFTs and activated hypertrophic microglia in association with low neuron densities suggest they may collectively contribute to focal neurodegeneration characteristic of PPA-AD.
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