Peripheral complement interactions with amyloid β peptide: Erythrocyte clearance mechanisms

被引：38

作者：

Brubaker, William D. ^{[1
]}

Crane, Andres ^{[1
]}

Johansson, Jenny U. ^{[1
]}

Yen, Kevin ^{[1
]}

Garfinkel, Kristina ^{[1
]}

Mastroeni, Diego ^{[2
,6
,7
]}

Asok, Priya ^{[1
]}

Bradt, Bonnie ^{[1
]}

Sabbagh, Marwan ^{[2
,8
]}

Wallace, Tanya L. ^{[1
,9
]}

Glavis-Bloom, Courtney ^{[1
,10
]}

Tenner, Andrea J. ^{[3
,4
,5
]}

Rogers, Joseph ^{[1
]}

机构：

[1] SRI Int, Ctr Neurosci, 333 Ravenswood Ave, Menlo Pk, CA 94025 USA

[2] Banner Sun Hlth Res Inst, LJ Roberts Ctr Alzheimers Res, Sun City, AZ USA

[3] Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92717 USA

[4] Univ Calif Irvine, Dept Pathol & Lab Med, Irvine, CA USA

[5] Univ Calif Irvine, Dept Neurobiol & Behav, Irvine, CA USA

[6] Arizona State Univ, Biodesign Inst, ASU Banner Neurodegenerat Dis Res Ctr, Tempe, AZ 85281 USA

[7] Arizona State Univ, Sch Life Sci, Tempe, AZ 85281 USA

[8] Barrow Neurol Inst, Alzheimers & Memory Disorders Div, 350 West Thomas Rd, Phoenix, AZ 85013 USA

[9] Blackthorn Therapeut, 329 Oyster Point Blvd, San Francisco, CA 94080 USA

[10] Dart NeuroSci, 12,278 Scripps Summit Dr, San Diego, CA 92131 USA

来源：

ALZHEIMERS & DEMENTIA | 2017年 / 13卷 / 12期

基金：

美国国家卫生研究院;

关键词：

Alzheimer's disease; Amyloid beta peptide; Complement; Complement receptor 1; Immune adherence; Blood; Erythrocyte; Human; BLOOD-BRAIN-BARRIER; GENOME-WIDE ASSOCIATION; ALZHEIMERS-DISEASE; CEREBROSPINAL-FLUID; IDENTIFIES VARIANTS; MOUSE MODEL; CR-1; PLASMA; SERUM; AUTOANTIBODIES;

D O I：

10.1016/j.jalz.2017.03.010

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Introduction: Although amyloid beta peptide (A beta) 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 A beta by erythrocytes and its deficiency in Alzheimer's disease (AD). Results: A beta was shown to be subject to immune adherence at every step in the pathway. A beta dose-dependently activated serum complement. Complement-opsonized A beta was captured by erythrocytes via CR1. Erythrocytes, A beta, and hepatic Kupffer cells were colocalized in the human liver. Significant deficits in erythrocyte A beta 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. (C) 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

引用

页码：1397 / 1409

页数：13

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