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)...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Mar Cuadrado-Tejedor, Marta Pérez-González, Rocío Alfaro-Ruiz, Sara Badesso, Diego Sucunza, María Espelosin, Susana Ursúa, Mercedes Lachen-Montes, Joaquín Fernández-Irigoyen, Enrique Santamaria, Rafael Luján, Ana García-Osta
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	Alzheimer’s disease amyloid hTauP301L mitochondria Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/45bc2d24362b4bc7b3686373aa045241
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:45bc2d24362b4bc7b3686373aa045241
record_format	dspace
spelling	oai:doaj.org-article:45bc2d24362b4bc7b3686373aa0452412021-11-11T17:22:06ZAmyloid-Driven Tau Accumulation on Mitochondria Potentially Leads to Cognitive Deterioration in Alzheimer’s Disease10.3390/ijms2221119501422-00671661-6596https://doaj.org/article/45bc2d24362b4bc7b3686373aa0452412021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11950https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Despite 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 <i>tau</i>, was injected into the dorsal hippocampi of APP/PS1 transgenic mice or <i>wild type</i> 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.Mar Cuadrado-TejedorMarta Pérez-GonzálezRocío Alfaro-RuizSara BadessoDiego SucunzaMaría EspelosinSusana UrsúaMercedes Lachen-MontesJoaquín Fernández-IrigoyenEnrique SantamariaRafael LujánAna García-OstaMDPI AGarticleAlzheimer’s diseaseamyloidhTauP301LmitochondriaBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11950, p 11950 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Alzheimer’s disease amyloid hTauP301L mitochondria Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	Alzheimer’s disease amyloid hTauP301L mitochondria Biology (General) QH301-705.5 Chemistry QD1-999 Mar Cuadrado-Tejedor Marta Pérez-González Rocío Alfaro-Ruiz Sara Badesso Diego Sucunza María Espelosin Susana Ursúa Mercedes Lachen-Montes Joaquín Fernández-Irigoyen Enrique Santamaria Rafael Luján Ana García-Osta Amyloid-Driven Tau Accumulation on Mitochondria Potentially Leads to Cognitive Deterioration in Alzheimer’s Disease
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 <i>tau</i>, was injected into the dorsal hippocampi of APP/PS1 transgenic mice or <i>wild type</i> 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	article
author	Mar Cuadrado-Tejedor Marta Pérez-González Rocío Alfaro-Ruiz Sara Badesso Diego Sucunza María Espelosin Susana Ursúa Mercedes Lachen-Montes Joaquín Fernández-Irigoyen Enrique Santamaria Rafael Luján Ana García-Osta
author_facet	Mar Cuadrado-Tejedor Marta Pérez-González Rocío Alfaro-Ruiz Sara Badesso Diego Sucunza María Espelosin Susana Ursúa Mercedes Lachen-Montes Joaquín Fernández-Irigoyen Enrique Santamaria Rafael Luján Ana García-Osta
author_sort	Mar Cuadrado-Tejedor
title	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_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_sort	amyloid-driven tau accumulation on mitochondria potentially leads to cognitive deterioration in alzheimer’s disease
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/45bc2d24362b4bc7b3686373aa045241
work_keys_str_mv	AT marcuadradotejedor amyloiddriventauaccumulationonmitochondriapotentiallyleadstocognitivedeteriorationinalzheimersdisease AT martaperezgonzalez amyloiddriventauaccumulationonmitochondriapotentiallyleadstocognitivedeteriorationinalzheimersdisease AT rocioalfaroruiz amyloiddriventauaccumulationonmitochondriapotentiallyleadstocognitivedeteriorationinalzheimersdisease AT sarabadesso amyloiddriventauaccumulationonmitochondriapotentiallyleadstocognitivedeteriorationinalzheimersdisease AT diegosucunza amyloiddriventauaccumulationonmitochondriapotentiallyleadstocognitivedeteriorationinalzheimersdisease AT mariaespelosin amyloiddriventauaccumulationonmitochondriapotentiallyleadstocognitivedeteriorationinalzheimersdisease AT susanaursua amyloiddriventauaccumulationonmitochondriapotentiallyleadstocognitivedeteriorationinalzheimersdisease AT mercedeslachenmontes amyloiddriventauaccumulationonmitochondriapotentiallyleadstocognitivedeteriorationinalzheimersdisease AT joaquinfernandezirigoyen amyloiddriventauaccumulationonmitochondriapotentiallyleadstocognitivedeteriorationinalzheimersdisease AT enriquesantamaria amyloiddriventauaccumulationonmitochondriapotentiallyleadstocognitivedeteriorationinalzheimersdisease AT rafaellujan amyloiddriventauaccumulationonmitochondriapotentiallyleadstocognitivedeteriorationinalzheimersdisease AT anagarciaosta amyloiddriventauaccumulationonmitochondriapotentiallyleadstocognitivedeteriorationinalzheimersdisease
_version_	1718432113631428608

Amyloid-Driven Tau Accumulation on Mitochondria Potentially Leads to Cognitive Deterioration in Alzheimer’s Disease

Ejemplares similares