La patología de granos argirófilos y la taupatía de tipo Alzheimer: características comunes y diferenciales

Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 04-02-2014

Bibliographic Details
Author: Rábano, Alberto
Format: doctoral thesis
Publication Date:2014
Country:España
Institution:Universidad Autónoma de Madrid
Repository:Biblos-e Archivo. Repositorio Institucional de la UAM
Language:Spanish
OAI Identifier:oai:repositorio.uam.es:10486/660597
Online Access:http://hdl.handle.net/10486/660597
Access Level:Open access
Keyword:Proteina tau - Tesis doctorales
Alzheimer, Enfermedad de - Tesis doctorales
Biología y Biomedicina / Biología
id ES_a70b1d9941e68de1fda0d75d8cab2c5b
oai_identifier_str oai:repositorio.uam.es:10486/660597
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv La patología de granos argirófilos y la taupatía de tipo Alzheimer: características comunes y diferenciales
title La patología de granos argirófilos y la taupatía de tipo Alzheimer: características comunes y diferenciales
spellingShingle La patología de granos argirófilos y la taupatía de tipo Alzheimer: características comunes y diferenciales
Rábano, Alberto
Proteina tau - Tesis doctorales
Alzheimer, Enfermedad de - Tesis doctorales
Biología y Biomedicina / Biología
title_short La patología de granos argirófilos y la taupatía de tipo Alzheimer: características comunes y diferenciales
title_full La patología de granos argirófilos y la taupatía de tipo Alzheimer: características comunes y diferenciales
title_fullStr La patología de granos argirófilos y la taupatía de tipo Alzheimer: características comunes y diferenciales
title_full_unstemmed La patología de granos argirófilos y la taupatía de tipo Alzheimer: características comunes y diferenciales
title_sort La patología de granos argirófilos y la taupatía de tipo Alzheimer: características comunes y diferenciales
dc.creator.none.fl_str_mv Rábano, Alberto
author Rábano, Alberto
author_facet Rábano, Alberto
author_role author
dc.contributor.none.fl_str_mv Ávila de Grado, Jesús
Departamento de Biología Molecular
Facultad de Ciencias
dc.subject.none.fl_str_mv Proteina tau - Tesis doctorales
Alzheimer, Enfermedad de - Tesis doctorales
Biología y Biomedicina / Biología
topic Proteina tau - Tesis doctorales
Alzheimer, Enfermedad de - Tesis doctorales
Biología y Biomedicina / Biología
description Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 04-02-2014
publishDate 2014
dc.date.none.fl_str_mv 2014
2014-02-04
dc.type.none.fl_str_mv doctoral thesis
http://purl.org/coar/resource_type/c_db06
NA
http://purl.org/coar/version/c_be7fb7dd8ff6fe43
dc.type.openaire.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/660597
url http://hdl.handle.net/10486/660597
dc.language.none.fl_str_mv Español
spa
language_invalid_str_mv Español
language spa
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869415746416672768
spelling La patología de granos argirófilos y la taupatía de tipo Alzheimer: características comunes y diferencialesRábano, AlbertoProteina tau - Tesis doctoralesAlzheimer, Enfermedad de - Tesis doctoralesBiología y Biomedicina / BiologíaTesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 04-02-2014Argyrophylic grain disease (AGD) is a sporadic 4R tauopathy that usually presents in combination with other sporadic tauopathies or with Alzheimer’s disease (AD) pathology, and may contribute to dementia in older age patients. In previous studies, a detailed analysis of AGD pathology in the medial temporal lobe has been hampered by the common presence of concurrent Alzheimer’s changes. With the objective to assess the potentiality of AGD in research on tau pathogenesis and propagation, here we present a study of a series of AGD postmortem cases (n = 53), selected from a reference series of 511 brains donated to 3 brain banks in Spain. All cases were thoroughly evaluated according to consensus neuropathological methods and protocols. A detailed neuropathological evaluation of the medial temporal lobe was accomplished at three coronal levels with Gallyas stain, p62, AT8 and AT100 antibodies. A subgroup of cases with Braak‐stage ≤ II (n = 23) was selected for detailed morphological and molecular study. Western blot analysis of the entorhinal and hippocampal cortex was performed in 8 cases with a panel of anti‐tau antibodies. Cases were genotyped for APOE polymorphism and for H1/H2 alleles of the MAPT gene. All cases, and particularly lower‐Braak stage cases, displayed a highly homogeneous pattern of involvement by argyrophylic grains and pretangles between connected regions (primarily, basolateral nuclei of the amygdala, entorhinal/transentorhinal cortex, hippocampal cortex). Staging of cases reveals progression of pathology along well‐established neuroanatomical pathways, with independence of the progression of Alzheimer’s type pathology (either tau or β‐amyloid pathology). Western blot studies yielded a specific pattern of isoforms with a characteristic predominant band at 64k. Genetic analysis showed a strong association to the H1 allele of the MAPT gene. AGD may thus be an optimal natural disease model for testing hypotheses related to tau propagation in human tissue. Additionally, the entorhinal cortex of 6 control brains was studied in order to establish the differential features of the upper layers, where the earliest cell lesions of Alzheimer’s type and argyrophylic grain pathologies develop. To define the molecular characteristics of these neuron populations, microarrays were used to define the gene expression in that region. In this way, we identified several genes that are expressed distinctly in the upper and lower layers of the entorhinal cortex. These include the genes encoding the matrix Gla protein, collagen type 1_2, reelin, semaphorin 3C or the relaxin receptor, all related to the extracellular matrix. Thus, differences in the extracellular matrix components between the upper and lower layers of the entorhinal cortex may in part explain the vulnerability of neurons present in the upper layers of this brain region in disorders like Alzheimer’s disease or argyrophylic grain disease. In a further study here included 5 brains with Alzheimer’s type pathology were studied using intracellular injections of Lucifer yellow in fixed tissue to analyse over 19500 dendritic spines that were completely reconstructed in three dimensions along the length of the basal dendrites of pyramidal neurons in the parahippocampal cortex and CA1. Following intracellular injection, sections were immunostained for anti‐Lucifer yellow and with tau monoclonal antibodies AT8 and PHF‐1. We observed that the diffuse accumulation of phospho‐tau in a putative pre‐tangle state did not induce changes in the dendrites of pyramidal neurons, whereas the presence of tau aggregates forming intraneuronal neurofibrillary tangles was associated with progressive alteration of dendritic spines (loss of dendritic spines and changes in their morphology) and dendrite atrophy, depending on the degree of tangle development.Ávila de Grado, JesúsDepartamento de Biología MolecularFacultad de Ciencias20142014-02-04doctoral thesishttp://purl.org/coar/resource_type/c_db06NAhttp://purl.org/coar/version/c_be7fb7dd8ff6fe43info:eu-repo/semantics/doctoralThesisapplication/pdfhttp://hdl.handle.net/10486/660597reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridEspañolspaopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/6605972026-06-23T12:46:27Z
score 15,198674

Similar Items