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P3–432: Nanomolar concentrations of β–amyloid aggregates reduce spontaneous synaptic activity in hippocampal neurons
Author(s) -
Parodi Jorge L.,
Sepulveda Fernando,
Aguayo Luis
Publication year - 2006
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2006.05.1703
Subject(s) - hippocampal formation , neurodegeneration , calcium , synaptic vesicle , chemistry , neuroscience , biophysics , medicine , endocrinology , biology , vesicle , biochemistry , disease , membrane
neuronal lesions in various neurodegenerative diseases, including Lewy bodies in Parkinson’s disease. The presence of p62 in glial lesions, particularly in tauopathies where glial lesions are common, has not been specifically addressed. Objective: In the present study, we used immunohistochemistry and confocal microscopy to investigate the role of p62 in glial inclusions in 3R and 4R tauopathies, including tufted astrocytes in progressive supranuclear palsy (PSP), astrocytic plaques in corticobasal degeneration (CBD), ramified astrocytes in Pick’s disease (PiD) and coiled bodies. Thorn-shaped astrocytes, which can be found in normal elderly, and neuronal lesions, including neurofibrillary tangles, Pick bodies and ballooned neurons, were also studied. Methods: Single and double immunolabeling was performed for tau and p62 and for ubiquitin and p62. Results: Ubiquitin-negative, p62-positive glial and neuronal lesions were common in the 4R tauopathies of PSP and CBD, while there was more co-localization of ubiquitin and p62 in PiD, a 3R tauopathy. Astrocytic lesions in PSP, CBD and PiD that are composed of filamentous tau had similar immunoreactive profiles, suggesting a common disease mechanism. In contrast, thorn-shaped astrocytes, which are nonfilamentous, tau-immunoreactive lesions, were negative for both ubiquitin and p62. Conclusions: The findings indicate that p62 is a marker for filamentous protein aggregates in a range of neurodegenerative disorders in both neurons and glia and further suggest a role for the ubiquitin proteasomal system in filamentous neuronal and glial lesions.