Alzheimer disease macrophages shuttle amyloid-beta from neurons to vessels, contributing to amyloid angiopathy.

Abstract:

:Neuronal accumulation of oligomeric amyloid-beta (Alphabeta) is considered the proximal cause of neuronal demise in Alzheimer disease (AD) patients. Blood-borne macrophages might reduce Abeta stress to neurons by immigration into the brain and phagocytosis of Alphabeta. We tested migration and export across a blood-brain barrier model, and phagocytosis and clearance of Alphabeta by AD and normal subjects' macrophages. Both AD and normal macrophages were inhibited in Alphabeta export across the blood-brain barrier due to adherence of Abeta-engorged macrophages to the endothelial layer. In comparison to normal subjects' macrophages, AD macrophages ingested and cleared less Alphabeta, and underwent apoptosis upon exposure to soluble, protofibrillar, or fibrillar Alphabeta. Confocal microscopy of stained AD brain sections revealed oligomeric Abeta in neurons and apoptotic macrophages, which surrounded and infiltrated congophilic microvessels, and fibrillar Abeta in plaques and microvessel walls. After incubation with AD brain sections, normal subjects' monocytes intruded into neurons and uploaded oligomeric Abeta. In conclusion, in patients with AD, macrophages appear to shuttle Abeta from neurons to vessels where their apoptosis may release fibrillar Abeta, contributing to cerebral amyloid angiopathy.

journal_name

Acta Neuropathol

journal_title

Acta neuropathologica

authors

Zaghi J,Goldenson B,Inayathullah M,Lossinsky AS,Masoumi A,Avagyan H,Mahanian M,Bernas M,Weinand M,Rosenthal MJ,Espinosa-Jeffrey A,de Vellis J,Teplow DB,Fiala M

doi

10.1007/s00401-008-0481-0

subject

Has Abstract

pub_date

2009-02-01 00:00:00

pages

111-24

issue

2

eissn

0001-6322

issn

1432-0533

journal_volume

117

pub_type

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