Association of CD2AP neuronal deposits with Braak neurofibrillary stage in Alzheimer's disease
Genome-wide association studies have described several genes as genetic susceptibility loci for Alzheimer's disease (AD). Among them, CD2AP encodes CD2-associated protein, a scaffold protein implicated in dynamic actin remodeling and membrane trafficking during endocytosis and cytokinesis. Alth...
| Autores: | , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2021 |
| País: | España |
| Institución: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:ddd.uab.cat:292289 |
| Acceso en línea: | https://ddd.uab.cat/record/292289 https://dx.doi.org/urn:doi:10.1111/bpa.13016 |
| Access Level: | acceso abierto |
| Palabra clave: | Alzheimer's disease CD2AP Neurofibrillary tangles Pick's disease Tau Tauopathies |
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Association of CD2AP neuronal deposits with Braak neurofibrillary stage in Alzheimer's diseaseCamacho, Jessica|||0000-0001-8018-8274Rábano, Alberto|||0000-0001-9320-6566Marazuela, Paula|||0000-0003-1038-5242Bonaterra-Pastra, Anna|||0000-0002-1480-622XSerna, Garazi|||0000-0003-2666-0982Moliné, Teresa|||0000-0003-4912-5114Ramón y Cajal, Santiago|||0000-0002-3867-1390Martinez-Saez, Elena|||0000-0001-6004-5364Hernandez Guillamon, Maria Mar|||0000-0001-8844-0091Alzheimer's diseaseCD2APNeurofibrillary tanglesPick's diseaseTauTauopathiesGenome-wide association studies have described several genes as genetic susceptibility loci for Alzheimer's disease (AD). Among them, CD2AP encodes CD2-associated protein, a scaffold protein implicated in dynamic actin remodeling and membrane trafficking during endocytosis and cytokinesis. Although a clear link between CD2AP defects and glomerular pathology has been described, little is known about the function of CD2AP in the brain. The aim of this study was to analyze the distribution of CD2AP in the AD brain and its potential associations with tau aggregation and β-amyloid (Aβ) deposition. First, we performed immunohistochemical analysis of CD2AP expression in brain tissue from AD patients and controls (N = 60). Our results showed granular CD2AP immunoreactivity in the human brain endothelium in all samples. In AD cases, no CD2AP was found to be associated with Aβ deposits in vessels or parenchymal plaques. CD2AP neuronal inclusions similar to neurofibrillary tangles (NFT) and neuropil thread-like deposits were found only in AD samples. Moreover, immunofluorescence analysis revealed that CD2AP colocalized with pTau. Regarding CD2AP neuronal distribution, a hierarchical progression from the entorhinal to the temporal and occipital cortex was detected. We found that CD2AP immunodetection in neurons was strongly and positively associated with Braak neurofibrillary stage, independent of age and other pathological hallmarks. To further investigate the association between pTau and CD2AP, we included samples from cases of primary tauopathies (corticobasal degeneration [CBD], progressive supranuclear palsy [PSP], and Pick's disease [PiD]) in our study. Among these cases, CD2AP positivity was only found in PiD samples as neurofibrillary tangle-like and Pick body-like deposits, whereas no neuronal CD2AP deposits were detected in PSP or CBD samples, which suggested an association of CD2AP neuronal expression with 3R-Tau-diseases. In conclusion, our findings open a new road to investigate the complex cellular mechanism underlying the tangle conformation and tau pathology in the brain.Universitat Autònoma de Barcelona 22021-01-0120212021-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/292289https://dx.doi.org/urn:doi:10.1111/bpa.13016reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengInstituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI17/00275Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI20/00465Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 RD16/0019/0021open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2922892026-06-06T12:50:31Z |
| dc.title.none.fl_str_mv |
Association of CD2AP neuronal deposits with Braak neurofibrillary stage in Alzheimer's disease |
| title |
Association of CD2AP neuronal deposits with Braak neurofibrillary stage in Alzheimer's disease |
| spellingShingle |
Association of CD2AP neuronal deposits with Braak neurofibrillary stage in Alzheimer's disease Camacho, Jessica|||0000-0001-8018-8274 Alzheimer's disease CD2AP Neurofibrillary tangles Pick's disease Tau Tauopathies |
| title_short |
Association of CD2AP neuronal deposits with Braak neurofibrillary stage in Alzheimer's disease |
| title_full |
Association of CD2AP neuronal deposits with Braak neurofibrillary stage in Alzheimer's disease |
| title_fullStr |
Association of CD2AP neuronal deposits with Braak neurofibrillary stage in Alzheimer's disease |
| title_full_unstemmed |
Association of CD2AP neuronal deposits with Braak neurofibrillary stage in Alzheimer's disease |
| title_sort |
Association of CD2AP neuronal deposits with Braak neurofibrillary stage in Alzheimer's disease |
| dc.creator.none.fl_str_mv |
Camacho, Jessica|||0000-0001-8018-8274 Rábano, Alberto|||0000-0001-9320-6566 Marazuela, Paula|||0000-0003-1038-5242 Bonaterra-Pastra, Anna|||0000-0002-1480-622X Serna, Garazi|||0000-0003-2666-0982 Moliné, Teresa|||0000-0003-4912-5114 Ramón y Cajal, Santiago|||0000-0002-3867-1390 Martinez-Saez, Elena|||0000-0001-6004-5364 Hernandez Guillamon, Maria Mar|||0000-0001-8844-0091 |
| author |
Camacho, Jessica|||0000-0001-8018-8274 |
| author_facet |
Camacho, Jessica|||0000-0001-8018-8274 Rábano, Alberto|||0000-0001-9320-6566 Marazuela, Paula|||0000-0003-1038-5242 Bonaterra-Pastra, Anna|||0000-0002-1480-622X Serna, Garazi|||0000-0003-2666-0982 Moliné, Teresa|||0000-0003-4912-5114 Ramón y Cajal, Santiago|||0000-0002-3867-1390 Martinez-Saez, Elena|||0000-0001-6004-5364 Hernandez Guillamon, Maria Mar|||0000-0001-8844-0091 |
| author_role |
author |
| author2 |
Rábano, Alberto|||0000-0001-9320-6566 Marazuela, Paula|||0000-0003-1038-5242 Bonaterra-Pastra, Anna|||0000-0002-1480-622X Serna, Garazi|||0000-0003-2666-0982 Moliné, Teresa|||0000-0003-4912-5114 Ramón y Cajal, Santiago|||0000-0002-3867-1390 Martinez-Saez, Elena|||0000-0001-6004-5364 Hernandez Guillamon, Maria Mar|||0000-0001-8844-0091 |
| author2_role |
author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Universitat Autònoma de Barcelona |
| dc.subject.none.fl_str_mv |
Alzheimer's disease CD2AP Neurofibrillary tangles Pick's disease Tau Tauopathies |
| topic |
Alzheimer's disease CD2AP Neurofibrillary tangles Pick's disease Tau Tauopathies |
| description |
Genome-wide association studies have described several genes as genetic susceptibility loci for Alzheimer's disease (AD). Among them, CD2AP encodes CD2-associated protein, a scaffold protein implicated in dynamic actin remodeling and membrane trafficking during endocytosis and cytokinesis. Although a clear link between CD2AP defects and glomerular pathology has been described, little is known about the function of CD2AP in the brain. The aim of this study was to analyze the distribution of CD2AP in the AD brain and its potential associations with tau aggregation and β-amyloid (Aβ) deposition. First, we performed immunohistochemical analysis of CD2AP expression in brain tissue from AD patients and controls (N = 60). Our results showed granular CD2AP immunoreactivity in the human brain endothelium in all samples. In AD cases, no CD2AP was found to be associated with Aβ deposits in vessels or parenchymal plaques. CD2AP neuronal inclusions similar to neurofibrillary tangles (NFT) and neuropil thread-like deposits were found only in AD samples. Moreover, immunofluorescence analysis revealed that CD2AP colocalized with pTau. Regarding CD2AP neuronal distribution, a hierarchical progression from the entorhinal to the temporal and occipital cortex was detected. We found that CD2AP immunodetection in neurons was strongly and positively associated with Braak neurofibrillary stage, independent of age and other pathological hallmarks. To further investigate the association between pTau and CD2AP, we included samples from cases of primary tauopathies (corticobasal degeneration [CBD], progressive supranuclear palsy [PSP], and Pick's disease [PiD]) in our study. Among these cases, CD2AP positivity was only found in PiD samples as neurofibrillary tangle-like and Pick body-like deposits, whereas no neuronal CD2AP deposits were detected in PSP or CBD samples, which suggested an association of CD2AP neuronal expression with 3R-Tau-diseases. In conclusion, our findings open a new road to investigate the complex cellular mechanism underlying the tangle conformation and tau pathology in the brain. |
| publishDate |
2021 |
| dc.date.none.fl_str_mv |
2 2021-01-01 2021 2021-01-01 |
| dc.type.none.fl_str_mv |
Article http://purl.org/coar/resource_type/c_6501 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
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article |
| dc.identifier.none.fl_str_mv |
https://ddd.uab.cat/record/292289 https://dx.doi.org/urn:doi:10.1111/bpa.13016 |
| url |
https://ddd.uab.cat/record/292289 https://dx.doi.org/urn:doi:10.1111/bpa.13016 |
| dc.language.none.fl_str_mv |
Inglés eng |
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Inglés |
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eng |
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Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI17/00275 Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI20/00465 Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 RD16/0019/0021 |
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open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by-nc-nd/4.0/ |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by-nc-nd/4.0/ |
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openAccess |
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