STARD1 and NPC1 expression as pathological markers associated with astrogliosis in post-mortem brains from patients with Alzheimer's disease and Down syndrome.
Aging (Albany NY)
; 12(1): 571-592, 2020 01 05.
Article
em En
| MEDLINE
| ID: mdl-31902793
ABSTRACT
Alzheimer´s disease (AD) is a progressive neurodegenerative disorder of complex etiology, while Down syndrome (DS) is considered a genetically determined form of AD. Alterations in cholesterol homeostasis have been linked to AD although the role in this association is not well understood. Increased expression of STARD1 and NPC1, which are involved in intracellular cholesterol trafficking, has been reported in experimental AD models but not in patients with AD. Here we analyzed endolysosomal/mitochondrial cholesterol homeostasis, expression of NPC1 and STARD1 and correlation with pathological markers of AD in cortex and hippocampus from post-mortem brains from patients with AD and DS. NPC1 expression was observed in hippocampus from patients with AD and DS. Moreover, STARD1 expression increased in hippocampus and cortex from patients with AD and DS, respectively, and its immunoreactivity discriminated controls from AD or DS with a better accuracy than Aß42. Hippocampal areas stained with the recombinant GST-PFO probe showed increased mitochondrial cholesterol within astrocytes of brains from patients with AD and DS-brains compared to controls. Lysosomal cholesterol accumulation within hippocampal astrocytes was higher in DS than in AD. These data revealed increased intracellular cholesterol loading in hippocampus from patient with AD and DS and suggest that STARD1 could be a potential pre-clinical marker associated with early stages of AD pathology.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fosfoproteínas
/
Encéfalo
/
Expressão Gênica
/
Síndrome de Down
/
Peptídeos e Proteínas de Sinalização Intracelular
/
Doença de Alzheimer
/
Gliose
Tipo de estudo:
Risk_factors_studies
Limite:
Female
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article