Abnormal Tau Phosphorylation in the Thorny Excrescences of CA3 Hippocampal Neurons in Patients with Alzheimer's Disease

A key symptom in the early stages of Alzheimer's disease (AD) is the loss of declarative memory. The anatomical substrate that supports this kind of memory involves the neural circuits of the medial temporal lobe, and in particular, of the hippocampal formation and adjacent cortex. A main featu...

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Autores: Blázquez-Llorca, Lidia, García-Marín, Virginia, Merino-Serrais, Paula, Ávila, Jesús, DeFelipe, Javier
Tipo de recurso: artículo
Fecha de publicación:2011
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/57129
Acceso en línea:http://hdl.handle.net/10261/57129
Access Level:acceso abierto
Palabra clave:Axons
Mossy Fibers
Phosphorilation
Alzheimer disease
Glutamatergic terminals
Hippocampal formation
Tau protein
Thorny excrescences
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spelling Abnormal Tau Phosphorylation in the Thorny Excrescences of CA3 Hippocampal Neurons in Patients with Alzheimer's DiseaseBlázquez-Llorca, LidiaGarcía-Marín, VirginiaMerino-Serrais, PaulaÁvila, JesúsDeFelipe, JavierAxonsMossy FibersPhosphorilationAlzheimer diseaseGlutamatergic terminalsHippocampal formationTau proteinThorny excrescencesA key symptom in the early stages of Alzheimer's disease (AD) is the loss of declarative memory. The anatomical substrate that supports this kind of memory involves the neural circuits of the medial temporal lobe, and in particular, of the hippocampal formation and adjacent cortex. A main feature of AD is the abnormal phosphorylation of the tau protein and the presence of tangles. The sequence of cellular changes related to tau phosphorylation and tangle formation has been studied with an antibody that binds to diffuse phosphotau (AT8). Moreover, another tau antibody (PHF-1) has been used to follow the pathway of neurofibrillary (tau aggregation) degeneration in AD. We have used a variety of quantitative immunocytochemical techniques and confocal microscopy to visualize and characterize neurons labeled with AT8 and PHF-1 antibodies. We present here the rather unexpected discovery that in AD, there is conspicuous abnormal phosphorylation of the tau protein in a selective subset of dendritic spines. We identified these spines as the typical thorny excrescences of hippocampal CA3 neurons in a pre-tangle state. Since thorny excrescences represent a major synaptic target of granule cell axons (mossy fibers), such aberrant phosphorylation may play an essential role in the memory impairment typical of AD patients.Thisworkwas supported by grants from the following entities: CIBERNED (CB06/05/0066), Fundación CIEN (Financiación de Proyectos de Investigación de Enfermedad de Alzheimer y enfermedades relacionadas 2008), Fundación Caixa (BM05-47-0), the Spanish Ministerio de Ciencia e Innovación (SAF2009-09394).Peer reviewedIOS PressCentro Investigación Biomédica en Red Enfermedades Neurodegenerativas (España)Fundación Centro de Investigación de Enfermedades NeurológicasFundación la CaixaMinisterio de Ciencia e Innovación (España)201220122011info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501http://hdl.handle.net/10261/57129reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.3233/JAD-2011-110659info:eu-repo/semantics/openAccessoai:digital.csic.es:10261/571292026-05-22T06:33:51Z
dc.title.none.fl_str_mv Abnormal Tau Phosphorylation in the Thorny Excrescences of CA3 Hippocampal Neurons in Patients with Alzheimer's Disease
title Abnormal Tau Phosphorylation in the Thorny Excrescences of CA3 Hippocampal Neurons in Patients with Alzheimer's Disease
spellingShingle Abnormal Tau Phosphorylation in the Thorny Excrescences of CA3 Hippocampal Neurons in Patients with Alzheimer's Disease
Blázquez-Llorca, Lidia
Axons
Mossy Fibers
Phosphorilation
Alzheimer disease
Glutamatergic terminals
Hippocampal formation
Tau protein
Thorny excrescences
title_short Abnormal Tau Phosphorylation in the Thorny Excrescences of CA3 Hippocampal Neurons in Patients with Alzheimer's Disease
title_full Abnormal Tau Phosphorylation in the Thorny Excrescences of CA3 Hippocampal Neurons in Patients with Alzheimer's Disease
title_fullStr Abnormal Tau Phosphorylation in the Thorny Excrescences of CA3 Hippocampal Neurons in Patients with Alzheimer's Disease
title_full_unstemmed Abnormal Tau Phosphorylation in the Thorny Excrescences of CA3 Hippocampal Neurons in Patients with Alzheimer's Disease
title_sort Abnormal Tau Phosphorylation in the Thorny Excrescences of CA3 Hippocampal Neurons in Patients with Alzheimer's Disease
dc.creator.none.fl_str_mv Blázquez-Llorca, Lidia
García-Marín, Virginia
Merino-Serrais, Paula
Ávila, Jesús
DeFelipe, Javier
author Blázquez-Llorca, Lidia
author_facet Blázquez-Llorca, Lidia
García-Marín, Virginia
Merino-Serrais, Paula
Ávila, Jesús
DeFelipe, Javier
author_role author
author2 García-Marín, Virginia
Merino-Serrais, Paula
Ávila, Jesús
DeFelipe, Javier
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Centro Investigación Biomédica en Red Enfermedades Neurodegenerativas (España)
Fundación Centro de Investigación de Enfermedades Neurológicas
Fundación la Caixa
Ministerio de Ciencia e Innovación (España)
dc.subject.none.fl_str_mv Axons
Mossy Fibers
Phosphorilation
Alzheimer disease
Glutamatergic terminals
Hippocampal formation
Tau protein
Thorny excrescences
topic Axons
Mossy Fibers
Phosphorilation
Alzheimer disease
Glutamatergic terminals
Hippocampal formation
Tau protein
Thorny excrescences
description A key symptom in the early stages of Alzheimer's disease (AD) is the loss of declarative memory. The anatomical substrate that supports this kind of memory involves the neural circuits of the medial temporal lobe, and in particular, of the hippocampal formation and adjacent cortex. A main feature of AD is the abnormal phosphorylation of the tau protein and the presence of tangles. The sequence of cellular changes related to tau phosphorylation and tangle formation has been studied with an antibody that binds to diffuse phosphotau (AT8). Moreover, another tau antibody (PHF-1) has been used to follow the pathway of neurofibrillary (tau aggregation) degeneration in AD. We have used a variety of quantitative immunocytochemical techniques and confocal microscopy to visualize and characterize neurons labeled with AT8 and PHF-1 antibodies. We present here the rather unexpected discovery that in AD, there is conspicuous abnormal phosphorylation of the tau protein in a selective subset of dendritic spines. We identified these spines as the typical thorny excrescences of hippocampal CA3 neurons in a pre-tangle state. Since thorny excrescences represent a major synaptic target of granule cell axons (mossy fibers), such aberrant phosphorylation may play an essential role in the memory impairment typical of AD patients.
publishDate 2011
dc.date.none.fl_str_mv 2011
2012
2012
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/57129
url http://hdl.handle.net/10261/57129
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.3233/JAD-2011-110659
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv IOS Press
publisher.none.fl_str_mv IOS Press
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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