Progression of Alzheimer's disease parallels unusual structural plasticity of human dentate granule cells.
Acta Neuropathol Commun
; 10(1): 125, 2022 08 29.
Article
em En
| MEDLINE
| ID: mdl-36038918
ABSTRACT
Alzheimer´s disease (AD), the most common form of dementia in industrialized countries, severely targets the hippocampal formation in humans and mouse models of this condition. The adult hippocampus hosts the continuous addition of new dentate granule cells (DGCs) in numerous mammalian species, including humans. Although the morphology and positioning of DGCs within the granule cell layer (GCL) match their developmental origin in rodents, a similar correlation has not been reported in humans to date. Our data reveal that DGCs located in inner portions of the human GCL show shorter and less complex dendrites than those found in outer portions of this layer, which are presumably generated developmentally. Moreover, in AD patients, DGCs show early morphological alterations that are further aggravated as the disease progresses. An aberrantly increased number of DGCs with several primary apical dendrites is the first morphological change detected in patients at Braak-Tau I/II stages. This alteration persists throughout AD progression and leads to generalized dendritic atrophy at late stages of the disease. Our data reveal the distinct vulnerability of several morphological characteristics of DGCs located in the inner and outer portions of the GCL to AD and support the notion that the malfunction of the hippocampus is related to cognitive impairments in patients with AD.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Giro Denteado
/
Doença de Alzheimer
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Animals
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Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article