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Amyloid-Driven Tau Accumulation on Mitochondria Potentially Leads to Cognitive Deterioration in Alzheimer’s Disease
Despite the well-accepted role of the two main neuropathological markers (β-amyloid and tau) in the progression of Alzheimer’s disease, the interaction and specific contribution of each of them is not fully elucidated. To address this question, in the present study, an adeno-associated virus (AAV9)...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584544/ https://www.ncbi.nlm.nih.gov/pubmed/34769380 http://dx.doi.org/10.3390/ijms222111950 |
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author | Cuadrado-Tejedor, Mar Pérez-González, Marta Alfaro-Ruiz, Rocío Badesso, Sara Sucunza, Diego Espelosin, María Ursúa, Susana Lachen-Montes, Mercedes Fernández-Irigoyen, Joaquín Santamaria, Enrique Luján, Rafael García-Osta, Ana |
author_facet | Cuadrado-Tejedor, Mar Pérez-González, Marta Alfaro-Ruiz, Rocío Badesso, Sara Sucunza, Diego Espelosin, María Ursúa, Susana Lachen-Montes, Mercedes Fernández-Irigoyen, Joaquín Santamaria, Enrique Luján, Rafael García-Osta, Ana |
author_sort | Cuadrado-Tejedor, Mar |
collection | PubMed |
description | Despite the well-accepted role of the two main neuropathological markers (β-amyloid and tau) in the progression of Alzheimer’s disease, the interaction and specific contribution of each of them is not fully elucidated. To address this question, in the present study, an adeno-associated virus (AAV9) carrying the mutant P301L form of human tau, was injected into the dorsal hippocampi of APP/PS1 transgenic mice or wild type mice (WT). Three months after injections, memory tasks, biochemical and immunohistochemical analysis were performed. We found that the overexpression of hTauP301L accelerates memory deficits in APP/PS1 mice, but it did not affect memory function of WT mice. Likewise, biochemical assays showed that only in the case of APP/PS1-hTauP301L injected mice, an important accumulation of tau was observed in the insoluble urea fraction. Similarly, electron microscopy images revealed that numerous clusters of tau immunoparticles appear at the dendrites of APP/PS1 injected mice and not in WT animals, suggesting that the presence of amyloid is necessary to induce tau aggregation. Interestingly, these tau immunoparticles accumulate in dendritic mitochondria in the APP/PS1 mice, whereas most of mitochondria in WT injected mice remain free of tau immunoparticles. Taken together, it seems that amyloid induces tau aggregation and accumulation in the dendritic mitochondria and subsequently may alter synapse function, thus, contributing to accelerate cognitive decline in APP/PS1 mice. |
format | Online Article Text |
id | pubmed-8584544 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-85845442021-11-12 Amyloid-Driven Tau Accumulation on Mitochondria Potentially Leads to Cognitive Deterioration in Alzheimer’s Disease Cuadrado-Tejedor, Mar Pérez-González, Marta Alfaro-Ruiz, Rocío Badesso, Sara Sucunza, Diego Espelosin, María Ursúa, Susana Lachen-Montes, Mercedes Fernández-Irigoyen, Joaquín Santamaria, Enrique Luján, Rafael García-Osta, Ana Int J Mol Sci Article Despite the well-accepted role of the two main neuropathological markers (β-amyloid and tau) in the progression of Alzheimer’s disease, the interaction and specific contribution of each of them is not fully elucidated. To address this question, in the present study, an adeno-associated virus (AAV9) carrying the mutant P301L form of human tau, was injected into the dorsal hippocampi of APP/PS1 transgenic mice or wild type mice (WT). Three months after injections, memory tasks, biochemical and immunohistochemical analysis were performed. We found that the overexpression of hTauP301L accelerates memory deficits in APP/PS1 mice, but it did not affect memory function of WT mice. Likewise, biochemical assays showed that only in the case of APP/PS1-hTauP301L injected mice, an important accumulation of tau was observed in the insoluble urea fraction. Similarly, electron microscopy images revealed that numerous clusters of tau immunoparticles appear at the dendrites of APP/PS1 injected mice and not in WT animals, suggesting that the presence of amyloid is necessary to induce tau aggregation. Interestingly, these tau immunoparticles accumulate in dendritic mitochondria in the APP/PS1 mice, whereas most of mitochondria in WT injected mice remain free of tau immunoparticles. Taken together, it seems that amyloid induces tau aggregation and accumulation in the dendritic mitochondria and subsequently may alter synapse function, thus, contributing to accelerate cognitive decline in APP/PS1 mice. MDPI 2021-11-04 /pmc/articles/PMC8584544/ /pubmed/34769380 http://dx.doi.org/10.3390/ijms222111950 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Cuadrado-Tejedor, Mar Pérez-González, Marta Alfaro-Ruiz, Rocío Badesso, Sara Sucunza, Diego Espelosin, María Ursúa, Susana Lachen-Montes, Mercedes Fernández-Irigoyen, Joaquín Santamaria, Enrique Luján, Rafael García-Osta, Ana Amyloid-Driven Tau Accumulation on Mitochondria Potentially Leads to Cognitive Deterioration in Alzheimer’s Disease |
title | Amyloid-Driven Tau Accumulation on Mitochondria Potentially Leads to Cognitive Deterioration in Alzheimer’s Disease |
title_full | Amyloid-Driven Tau Accumulation on Mitochondria Potentially Leads to Cognitive Deterioration in Alzheimer’s Disease |
title_fullStr | Amyloid-Driven Tau Accumulation on Mitochondria Potentially Leads to Cognitive Deterioration in Alzheimer’s Disease |
title_full_unstemmed | Amyloid-Driven Tau Accumulation on Mitochondria Potentially Leads to Cognitive Deterioration in Alzheimer’s Disease |
title_short | Amyloid-Driven Tau Accumulation on Mitochondria Potentially Leads to Cognitive Deterioration in Alzheimer’s Disease |
title_sort | amyloid-driven tau accumulation on mitochondria potentially leads to cognitive deterioration in alzheimer’s disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584544/ https://www.ncbi.nlm.nih.gov/pubmed/34769380 http://dx.doi.org/10.3390/ijms222111950 |
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