Preventive and therapeutic reduction of amyloid deposition and behavioral impairments in a model of Alzheimer's disease by whole blood exchange.
Mol Psychiatry
; 27(10): 4285-4296, 2022 10.
Article
em En
| MEDLINE
| ID: mdl-35835859
ABSTRACT
Alzheimer's disease (AD) is the major form of dementia in the elderly population. The main neuropathological changes in AD patients are neuronal death, synaptic alterations, brain inflammation, and the presence of cerebral protein aggregates in the form of amyloid plaques and neurofibrillary tangles. Compelling evidence suggests that the misfolding, aggregation, and cerebral deposition of amyloid-beta (Aß) plays a central role in the disease. Thus, prevention and removal of misfolded protein aggregates is considered a promising strategy to treat AD. In the present study, we describe that the development of cerebral amyloid plaques in a transgenic mice model of AD (Tg2576) was significantly reduced by 40-80% through exchanging whole blood with normal blood from wild type mice having the same genetic background. Importantly, such reduction resulted in improvement in spatial memory performance in aged Tg2576 mice. The exact mechanism by which blood exchange reduces amyloid pathology and improves memory is presently unknown, but measurements of Aß in plasma soon after blood exchange suggest that mobilization of Aß from the brain to blood may be implicated. Our results suggest that a target for AD therapy may exist in the peripheral circulation, which could open a novel disease-modifying intervention for AD.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Doença de Alzheimer
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article