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Deposition of amyloid β in the walls of human leptomeningeal arteries in relation to perivascular drainage pathways in cerebral amyloid angiopathy

Lookup NU author(s): Professor Johannes Attems, Professor Raj KalariaORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2015 The Authors. Deposition of amyloid β (Aβ) in the walls of cerebral arteries as cerebral amyloid angiopathy (CAA) suggests an age-related failure of perivascular drainage of soluble Aβ from the brain. As CAA is associated with Alzheimer's disease and with intracerebral haemorrhage, the present study determines the unique sequence of changes that occur as Aβ accumulates in artery walls. Paraffin sections of post-mortem human occipital cortex were immunostained for collagen IV, fibronectin, nidogen 2, Aβ and smooth muscle actin and the immunostaining was analysed using Image J and confocal microscopy. Results showed that nidogen 2 (entactin) increases with age and decreases in CAA. Confocal microscopy revealed stages in the progression of CAA: Aβ initially deposits in basement membranes in the tunica media, replaces first the smooth muscle cells and then the connective tissue elements to leave artery walls completely or focally replaced by Aβ. The pattern of development of CAA in the human brain suggests expansion of Aβ from the basement membranes to progressively replace all tissue elements in the artery wall. Establishing this full picture of the development of CAA is pivotal in understanding the clinical presentation of CAA and for developing therapies to prevent accumulation of Aβ in artery walls. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock.

Publication metadata

Author(s): Keable A, Fenna K, Yuen HM, Johnston DA, Smyth NR, Smith C, Salman RAS, Samarasekera N, Nicoll JAR, Attems J, Kalaria RN, Weller RO, Carare RO

Publication type: Article

Publication status: Published

Journal: Biochimica et Biophysica Acta - Molecular Basis of Disease

Year: 2016

Volume: 1862

Issue: 5

Pages: 1037-1046

Print publication date: 01/05/2016

Online publication date: 29/08/2015

Acceptance date: 26/08/2015

Date deposited: 20/04/2017

ISSN (print): 0925-4439

ISSN (electronic): 1879-260X

Publisher: Elsevier


DOI: 10.1016/j.bbadis.2015.08.024


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Funder referenceFunder name
Alzheimer's Research UK (ARUK-NCG2013B-1),
Biotechnology and Biological Sciences Research Council (UK) (BB/K015540/1),
Kirby Laing Foundation (3972/26414)
Newcastle Brain Tissue Resource, which is funded in part by a grant from the UK Medical Research Council (G0400074) and by Brains for Dementia research
Rosetrees Trust (M273)