@article{ddf8e3499d66448f87cebe71a6d1c9f0,
title = "Peripheral complement interactions with amyloid β peptide: Erythrocyte clearance mechanisms",
abstract = "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.",
keywords = "Alzheimer's disease, Amyloid β peptide, Blood, Complement, Complement receptor 1, Erythrocyte, Human, Immune adherence",
author = "Brubaker, {William D.} and Andr{\'e}s Crane and Johansson, {Jenny U.} and Kevin Yen and Kristina Garfinkel and Diego Mastroeni and Priya Asok and Bonnie Bradt and Marwan Sabbagh and Wallace, {Tanya L.} and Courtney Glavis-Bloom and Tenner, {Andrea J.} and Joseph Rogers",
note = "Funding Information: Experiments on human erythrocyte Aβ uptake were supported by the National Institute on Aging of the National Institutes of Health under grant number RO1AG07367. Experiments on human complement receptor 1 were supported by the National Institute on Aging of the National Institutes of Health under grant number RO1AG039750. Studies with nonhuman primates were supported by SRI International . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors thank Patrick McGeer, M.D., Ph.D.; James Gaio, Ph.D.; Michael Pangburn, Ph.D.; John Atkinson, Ph.D.; Douglas Walker, Ph.D.; and Lih-Fen Lue, Ph.D., for technical and other advice, as well as Thomas Beach, M.D., Ph.D., and Lucia Sue for provision of postmortem tissue samples. Funding Information: Experiments on human erythrocyte A? uptake were supported by the National Institute on Aging of the National Institutes of Health under grant number RO1AG07367. Experiments on human complement receptor 1 were supported by the National Institute on Aging of the National Institutes of Health under grant number RO1AG039750. Studies with nonhuman primates were supported by SRI International. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors thank Patrick McGeer, M.D., Ph.D.; James Gaio, Ph.D.; Michael Pangburn, Ph.D.; John Atkinson, Ph.D.; Douglas Walker, Ph.D.; and Lih-Fen Lue, Ph.D., for technical and other advice, as well as Thomas Beach, M.D., Ph.D., and Lucia Sue for provision of postmortem tissue samples. Publisher Copyright: {\textcopyright} 2017 the Alzheimer's Association",
year = "2017",
month = dec,
doi = "10.1016/j.jalz.2017.03.010",
language = "English (US)",
volume = "13",
pages = "1397--1409",
journal = "Alzheimer's and Dementia",
issn = "1552-5260",
publisher = "Elsevier Inc.",
number = "12",
}