Sequence of proteome profiles in preclinical and symptomatic Alzheimer's disease.
Alzheimers Dement
; 17(6): 946-958, 2021 06.
Article
em En
| MEDLINE
| ID: mdl-33871169
Proteome profile changes in Alzheimer's disease (AD) brains have been reported. However, it is unclear whether they represent a continuous process, or whether there is a sequential involvement of distinct proteins. To address this question, we used mass spectrometry. We analyzed soluble, dispersible, sodium dodecyl sulfate, and formic acid fractions of neocortex homogenates (mainly Brodmann area 17-19) from 18 pathologically diagnosed preclinical AD, 17 symptomatic AD, and 18 cases without signs of neurodegeneration. By doing so, we identified four groups of AD-related proteins being changed in levels in preclinical and symptomatic AD cases: early-responding, late-responding, gradually-changing, and fraction-shifting proteins. Gene ontology analysis of these proteins and all known AD-risk/causative genes identified vesicle endocytosis and the secretory pathway-related processes as an early-involved AD component. In conclusion, our findings suggest that subtle changes involving the secretory pathway and endocytosis precede severe proteome changes in symptomatic AD as part of the preclinical phase of AD. The respective early-responding proteins may also contribute to synaptic vesicle cycle alterations in symptomatic AD.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Encéfalo
/
Neocórtex
/
Proteoma
/
Doença de Alzheimer
/
Sintomas Prodrômicos
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Alzheimers Dement
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Bélgica
País de publicação:
Estados Unidos