Peripheral complement interactions with amyloid ß peptide: Erythrocyte clearance mechanisms.
Alzheimers Dement
; 13(12): 1397-1409, 2017 Dec.
Article
en En
| MEDLINE
| ID: mdl-28475854
ABSTRACT
INTRODUCTION:
Although amyloid ß peptide (Aß) is cleared from the brain to cerebrospinal fluid and the peripheral circulation, mechanisms for its removal from blood remain unresolved. Primates have uniquely evolved a highly effective peripheral clearance mechanism for pathogens, immune adherence, in which erythrocyte complement receptor 1 (CR1) plays a major role.METHODS:
Multidisciplinary methods were used to demonstrate immune adherence capture of Aß by erythrocytes and its deficiency in Alzheimer's disease (AD).RESULTS:
Aß was shown to be subject to immune adherence at every step in the pathway. Aß dose-dependently activated serum complement. Complement-opsonized Aß was captured by erythrocytes via CR1. Erythrocytes, Aß, and hepatic Kupffer cells were colocalized in the human liver. Significant deficits in erythrocyte Aß levels were found in AD and mild cognitive impairment patients.DISCUSSION:
CR1 polymorphisms elevate AD risk, and >80% of human CR1 is vested in erythrocytes to subserve immune adherence. The present results suggest that this pathway is pathophysiologically relevant in AD.Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Fragmentos de Péptidos
/
Receptores de Complemento
/
Péptidos beta-Amiloides
/
Eritrocitos
/
Enfermedad de Alzheimer
/
Disfunción Cognitiva
Tipo de estudio:
Observational_studies
/
Risk_factors_studies
Idioma:
En
Revista:
Alzheimers Dement
Año:
2017
Tipo del documento:
Article