Cell number changes in Alzheimer's disease relate to dementia, not to plaques and tangles

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art_POLICHISO_Cell_number_changes_in_Alzheimer_s_disease_relate_2013.PDF (1.39 MB)
Citações na Scopus
135
Tipo de produção
article
Data de publicação
2013
Editora
OXFORD UNIV PRESS
DOI
Indexadores
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Autores
ANDRADE-MORAES, Carlos Humberto
OLIVEIRA-PINTO, Ana V.
CASTRO-FONSECA, Emily
SILVA, Camila G. da
GUIMARAES, Daniel M.
SZCZUPAK, Diego
PARENTE-BRUNO, Danielle R.
CARVALHO, Ludmila R. B.
GOMES, Bruna V.
Autor de Grupo de pesquisa
Editores
Coordenadores
Organizadores
Citação
BRAIN, v.136, p.3738-3752, 2013
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Alzheimer's disease is the commonest cause of dementia in the elderly, but its pathological determinants are still debated. Amyloid-beta plaques and neurofibrillary tangles have been implicated either directly as disruptors of neural function, or indirectly by precipitating neuronal death and thus causing a reduction in neuronal number. Alternatively, the initial cognitive decline has been attributed to subtle intracellular events caused by amyloid-beta oligomers, resulting in dementia after massive synaptic dysfunction followed by neuronal degeneration and death. To investigate whether Alzheimer's disease is associated with changes in the absolute cell numbers of ageing brains, we used the isotropic fractionator, a novel technique designed to determine the absolute cellular composition of brain regions. We investigated whether plaques and tangles are associated with neuronal loss, or whether it is dementia that relates to changes of absolute cell composition, by comparing cell numbers in brains of patients severely demented with those of asymptomatic individuals-both groups histopathologically diagnosed as Alzheimer's-and normal subjects with no pathological signs of the disease. We found a great reduction of neuronal numbers in the hippocampus and cerebral cortex of demented patients with Alzheimer's disease, but not in asymptomatic subjects with Alzheimer's disease. We concluded that neuronal loss is associated with dementia and not the presence of plaques and tangles, which may explain why subjects with histopathological features of Alzheimer's disease can be asymptomatic; and exclude amyloid-beta deposits as causes for the reduction of neuronal numbers in the brain. We found an increase of non-neuronal cell numbers in the cerebral cortex and subcortical white matter of demented patients with Alzheimer's disease when compared with asymptomatic subjects with Alzheimer's disease and control subjects, suggesting a reactive glial cell response in the former that may be related to the symptoms they present.
Palavras-chave
ageing, dementia, isotropic fractionator
URI
https://observatorio.fm.usp.br/handle/OPI/5300
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Coleções
Artigos e Materiais de Revistas Científicas - LIM/22
Artigos e Materiais de Revistas Científicas - FM/MCM
Artigos e Materiais de Revistas Científicas - FM/MPT
Artigos e Materiais de Revistas Científicas - HC/ICHC