Naturally-Occurring Antibodies Against Bim are Decreased in Alzheimer's Disease and Attenuate AD-type Pathology in a Mouse Model.
Neurosci Bull
; 38(9): 1025-1040, 2022 Sep.
Article
em En
| MEDLINE
| ID: mdl-35570231
ABSTRACT
Increased neuronal apoptosis is an important pathological feature of Alzheimer's disease (AD). The Bcl-2-interacting mediator of cell death (Bim) mediates amyloid-beta (Aß)-induced neuronal apoptosis. Naturally-occurring antibodies against Bim (NAbs-Bim) exist in human blood, with their levels and functions unknown in AD. In this study, we found that circulating NAbs-Bim were decreased in AD patients. Plasma levels of NAbs-Bim were negatively associated with brain amyloid burden and positively associated with cognitive functions. Furthermore, NAbs-Bim purified from intravenous immunoglobulin rescued the behavioral deficits and ameliorated Aß deposition, tau hyperphosphorylation, microgliosis, and neuronal apoptosis in APP/PS1 mice. In vitro investigations demonstrated that NAbs-Bim were neuroprotective against AD through neutralizing Bim-directed neuronal apoptosis and the amyloidogenic processing of amyloid precursor protein. These findings indicate that the decrease of NAbs-Bim might contribute to the pathogenesis of AD and immunotherapies targeting Bim hold promise for the treatment of AD.
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Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
6_ODS3_enfermedades_notrasmisibles
Base de dados:
MEDLINE
Assunto principal:
Doença de Alzheimer
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Neurosci Bull
Ano de publicação:
2022
Tipo de documento:
Article