Peripheral complement interactions with amyloid β peptide: Erythrocyte clearance mechanisms
| Autor: | Diego Mastroeni, Tanya L. Wallace, Courtney Glavis-Bloom, Marwan N. Sabbagh, Andrea J. Tenner, Kevin Yen, Priya Asok, Joseph Rogers, Andrés Crane, William D. Brubaker, Kristina Garfinkel, Jenny U. Johansson, Bonnie Bradt |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Erythrocyte clearance biology Epidemiology Health Policy Complement receptor 1 P3 peptide Immune adherence Disease Amyloid β peptide Peripheral 03 medical and health sciences Psychiatry and Mental health Cellular and Molecular Neuroscience 030104 developmental biology 0302 clinical medicine Cerebrospinal fluid Developmental Neuroscience Immunology Neurology (clinical) Geriatrics and Gerontology biology.gene 030217 neurology & neurosurgery |
| Zdroj: | Alzheimer's & Dementia. 13:1397-1409 |
| ISSN: | 1552-5279 1552-5260 |
| Popis: | Introduction Although amyloid β peptide (Aβ) 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 Aβ by erythrocytes and its deficiency in Alzheimer's disease (AD). Results Aβ was shown to be subject to immune adherence at every step in the pathway. Aβ dose-dependently activated serum complement. Complement-opsonized Aβ was captured by erythrocytes via CR1. Erythrocytes, Aβ, and hepatic Kupffer cells were colocalized in the human liver. Significant deficits in erythrocyte Aβ 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. |
| Databáze: | OpenAIRE |
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