Association of CD2AP neuronal deposits with Braak neurofibrillary stage in Alzheimer's disease
Camacho, Jessica (Hospital Universitari Vall d'Hebron)
Rábano, Alberto (Fundación Centro de Investigación de Enfermedades Neurológicas (CIEN))
Marazuela, Paula (Vall d'Hebron Institut de Recerca (VHIR))
Bonaterra-Pastra, Anna (Vall d'Hebron Institut de Recerca (VHIR))
Serna, Garazi (Vall d'Hebron Institut d'Oncologia)
Moliné, Teresa (Hospital Universitari Vall d'Hebron)
Ramón y Cajal, Santiago (Hospital Universitari Vall d'Hebron)
Martinez-Saez, Elena (Hospital Universitari Vall d'Hebron)
Hernandez Guillamon, Maria Mar (Vall d'Hebron Institut de Recerca (VHIR))
Universitat Autònoma de Barcelona

Data:	2021
Resum:	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.
Ajuts:	Instituto de Salud Carlos III PI17/00275 Instituto de Salud Carlos III PI20/00465 Ministerio de Economía y Competitividad RD16/0019/0021
Drets:	Aquest 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.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Alzheimer's disease ; CD2AP ; Neurofibrillary tangles ; Pick's disease ; Tau ; Tauopathies
Publicat a:	Brain pathology, Vol. 32 (september 2021) , ISSN 1750-3639

DOI: 10.1111/bpa.13016
PMID: 34514662

16 p, 2.9 MB

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