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

Justin Zaghi, Ben Goldenson, Mohammed Inayathullah, Albert S. Lossinsky, Ava Masoumi, Hripsime Avagyan, Michelle Mahanian, Michael Bernas, Martin Weinand, Mark J. Rosenthal, Araceli Espinosa-Jeffrey, Jean Vellis, David B. Teplow, Milan Fiala

Research output: Contribution to journalArticle

72 Scopus citations

Abstract

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

Original languageEnglish (US)
Pages (from-to)111-124
Number of pages14
JournalActa Neuropathologica
Volume117
Issue number2
DOIs
StatePublished - 2009

Keywords

  • Alzheimer
  • Amyloid-beta
  • Angiopathy
  • Apoptosis
  • Congophillic
  • Macrophages

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Alzheimer disease macrophages shuttle amyloid-beta from neurons to vessels, contributing to amyloid angiopathy'. Together they form a unique fingerprint.

  • Cite this

    Zaghi, J., Goldenson, B., Inayathullah, M., Lossinsky, A. S., Masoumi, A., Avagyan, H., Mahanian, M., Bernas, M., Weinand, M., Rosenthal, M. J., Espinosa-Jeffrey, A., Vellis, J., Teplow, D. B., & Fiala, M. (2009). Alzheimer disease macrophages shuttle amyloid-beta from neurons to vessels, contributing to amyloid angiopathy. Acta Neuropathologica, 117(2), 111-124. https://doi.org/10.1007/s00401-008-0481-0