Microvascular Contributions to Alzheimer Disease Pathogenesis: Is Alzheimer Disease Primarily an Endotheliopathy?
Biomolecules
; 13(5)2023 05 13.
Article
em En
| MEDLINE
| ID: mdl-37238700
ABSTRACT
Alzheimer disease (AD) models are based on the notion that abnormal protein aggregation is the primary event in AD, which begins a decade or longer prior to symptom onset, and culminates in neurodegeneration; however, emerging evidence from animal and clinical studies suggests that reduced blood flow due to capillary loss and endothelial dysfunction are early and primary events in AD pathogenesis, which may precede amyloid and tau aggregation, and contribute to neuronal and synaptic injury via direct and indirect mechanisms. Recent data from clinical studies suggests that endothelial dysfunction is closely associated with cognitive outcomes in AD and that therapeutic strategies which promote endothelial repair in early AD may offer a potential opportunity to prevent or slow disease progression. This review examines evidence from clinical, imaging, neuropathological, and animal studies supporting vascular contributions to the onset and progression of AD pathology. Together, these observations support the notion that the onset of AD may be primarily influenced by vascular, rather than neurodegenerative, mechanisms and emphasize the importance of further investigations into the vascular hypothesis of AD.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Alzheimer
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Revista:
Biomolecules
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos