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Pathological tau signatures and nuclear alterations in neurons, astrocytes and microglia in Alzheimer's disease, progressive supranuclear palsy, and dementia with Lewy bodies

Accumulation of pathological tau aggregates is a prominent feature in tauopathies that leads during the course of the diseases to neuronal dysfunction before and cell death after. Microglia and astrocytes have been described as playing important roles in synaptic spreading of toxic tau in several ne...

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Autores principales: Montalbano, Mauro, Majmundar, Lajja, Sengupta, Urmi, Fung, Leiana, Kayed, Rakez
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9836371/
https://www.ncbi.nlm.nih.gov/pubmed/36054524
http://dx.doi.org/10.1111/bpa.13112
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author Montalbano, Mauro
Majmundar, Lajja
Sengupta, Urmi
Fung, Leiana
Kayed, Rakez
author_facet Montalbano, Mauro
Majmundar, Lajja
Sengupta, Urmi
Fung, Leiana
Kayed, Rakez
author_sort Montalbano, Mauro
collection PubMed
description Accumulation of pathological tau aggregates is a prominent feature in tauopathies that leads during the course of the diseases to neuronal dysfunction before and cell death after. Microglia and astrocytes have been described as playing important roles in synaptic spreading of toxic tau in several neurodegenerative diseases (NDs). Here, we have investigated the immunological and biochemical properties of aggregated tau species in different brain cell types in tau‐induced neurodegenerative diseases such as Alzheimer's disease (AD), progressive supranuclear palsy (PSP), and dementia with Lewy bodies (DLB). Additionally, we examined nuclear size, nuclear density, and chromatin compaction in neuronal and glial cells from diseased brain tissues. Microscopic‐histological examination was performed using in‐house mouse monoclonal antibodies for toxic tau conformers (TTC‐M1 and TTC‐M2) and tau oligomers (TOMA1‐4). By immunohistochemistry and co‐immunofluorescence assays using TOMA/TTC‐Ms and cell‐type specific markers for neurons, astrocytes, and microglia, we observed that TOMA/TTC‐Ms were immunoreactive to diverse tau species in different cell types. Analysis of colocalization coefficients indicated an increased pathological tau deposition mainly in the neurons. Western blot analysis of brain homogenates using TOMA/TTC‐Ms revealed distinct patterns of tau aggregation in each disease, suggesting that TOMA/TTC‐Ms can distinguish between different tau aggregates present in different tauopathies. Additionally, using DAPI staining, we observed that neuronal and astrocytic nuclei had significantly greater nuclear area and increased chromatin compaction in AD cortices compared to non‐demented controls. In contrast, reduction in nuclear density/area and more relaxed chromatin was noticed in DLB neurons, astrocytes and microglia and PSP astrocytes and microglia. Cell‐type specific tropism of toxic tau species in tauopathies will provide a greater understanding of the involvement of different brain cell types in tau pathology. In this study, we observed that each disease presented cell‐type specific nuclear phenotype and tau deposition pattern.
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spelling pubmed-98363712023-01-18 Pathological tau signatures and nuclear alterations in neurons, astrocytes and microglia in Alzheimer's disease, progressive supranuclear palsy, and dementia with Lewy bodies Montalbano, Mauro Majmundar, Lajja Sengupta, Urmi Fung, Leiana Kayed, Rakez Brain Pathol Research Articles Accumulation of pathological tau aggregates is a prominent feature in tauopathies that leads during the course of the diseases to neuronal dysfunction before and cell death after. Microglia and astrocytes have been described as playing important roles in synaptic spreading of toxic tau in several neurodegenerative diseases (NDs). Here, we have investigated the immunological and biochemical properties of aggregated tau species in different brain cell types in tau‐induced neurodegenerative diseases such as Alzheimer's disease (AD), progressive supranuclear palsy (PSP), and dementia with Lewy bodies (DLB). Additionally, we examined nuclear size, nuclear density, and chromatin compaction in neuronal and glial cells from diseased brain tissues. Microscopic‐histological examination was performed using in‐house mouse monoclonal antibodies for toxic tau conformers (TTC‐M1 and TTC‐M2) and tau oligomers (TOMA1‐4). By immunohistochemistry and co‐immunofluorescence assays using TOMA/TTC‐Ms and cell‐type specific markers for neurons, astrocytes, and microglia, we observed that TOMA/TTC‐Ms were immunoreactive to diverse tau species in different cell types. Analysis of colocalization coefficients indicated an increased pathological tau deposition mainly in the neurons. Western blot analysis of brain homogenates using TOMA/TTC‐Ms revealed distinct patterns of tau aggregation in each disease, suggesting that TOMA/TTC‐Ms can distinguish between different tau aggregates present in different tauopathies. Additionally, using DAPI staining, we observed that neuronal and astrocytic nuclei had significantly greater nuclear area and increased chromatin compaction in AD cortices compared to non‐demented controls. In contrast, reduction in nuclear density/area and more relaxed chromatin was noticed in DLB neurons, astrocytes and microglia and PSP astrocytes and microglia. Cell‐type specific tropism of toxic tau species in tauopathies will provide a greater understanding of the involvement of different brain cell types in tau pathology. In this study, we observed that each disease presented cell‐type specific nuclear phenotype and tau deposition pattern. John Wiley and Sons Inc. 2022-08-24 /pmc/articles/PMC9836371/ /pubmed/36054524 http://dx.doi.org/10.1111/bpa.13112 Text en © 2022 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Research Articles
Montalbano, Mauro
Majmundar, Lajja
Sengupta, Urmi
Fung, Leiana
Kayed, Rakez
Pathological tau signatures and nuclear alterations in neurons, astrocytes and microglia in Alzheimer's disease, progressive supranuclear palsy, and dementia with Lewy bodies
title Pathological tau signatures and nuclear alterations in neurons, astrocytes and microglia in Alzheimer's disease, progressive supranuclear palsy, and dementia with Lewy bodies
title_full Pathological tau signatures and nuclear alterations in neurons, astrocytes and microglia in Alzheimer's disease, progressive supranuclear palsy, and dementia with Lewy bodies
title_fullStr Pathological tau signatures and nuclear alterations in neurons, astrocytes and microglia in Alzheimer's disease, progressive supranuclear palsy, and dementia with Lewy bodies
title_full_unstemmed Pathological tau signatures and nuclear alterations in neurons, astrocytes and microglia in Alzheimer's disease, progressive supranuclear palsy, and dementia with Lewy bodies
title_short Pathological tau signatures and nuclear alterations in neurons, astrocytes and microglia in Alzheimer's disease, progressive supranuclear palsy, and dementia with Lewy bodies
title_sort pathological tau signatures and nuclear alterations in neurons, astrocytes and microglia in alzheimer's disease, progressive supranuclear palsy, and dementia with lewy bodies
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9836371/
https://www.ncbi.nlm.nih.gov/pubmed/36054524
http://dx.doi.org/10.1111/bpa.13112
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