Deposition of amyloid β in the walls of human leptomeningeal arteries in relation to perivascular drainage pathways in cerebral amyloid angiopathy.
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.
Faculty of Medicine, University of Southampton, Tremona Road, SO16 6YD, UK.
Abby
A
Keable
Faculty of Medicine, University of Southampton, Tremona Road, SO16 6YD, UK.
Kate
K
Fenna
Faculty of Medicine, University of Southampton, Tremona Road, SO16 6YD, UK.
Ho Ming
HM
Yuen
Faculty of Medicine, University of Southampton, Tremona Road, SO16 6YD, UK.
David A
DA
Johnston
Faculty of Medicine, University of Southampton, Tremona Road, SO16 6YD, UK.
Neil R
NR
Smyth
Centre for Clinical Brain Sciences, University of Edinburgh, UK.
Colin
C
Smith
Centre for Clinical Brain Sciences, University of Edinburgh, UK.
Rustam
R
Al-Shahi Salman
Centre for Clinical Brain Sciences, University of Edinburgh, UK.
Neshika
N
Samarasekera
Faculty of Medicine, University of Southampton, Tremona Road, SO16 6YD, UK.
James A R
JA
Nicoll
Institute of Neuroscience, Campus for Ageing and Vitality, Newcastle University, UK.
Johannes
J
Attems
Institute of Neuroscience, Campus for Ageing and Vitality, Newcastle University, UK.
Rajesh N
RN
Kalaria
Faculty of Medicine, University of Southampton, Tremona Road, SO16 6YD, UK.
Roy O
RO
Weller
Faculty of Medicine, University of Southampton, Tremona Road, SO16 6YD, UK. Electronic address: rcn@soton.ac.uk.
Roxana O
RO
Carare
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000378:metabolism*; D001485:Basement Membrane / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D016657:Cerebral Amyloid Angiopathy / Q000378:metabolism / Q000473:pathology*; D002536:Cerebral Arteries / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017540:Tunica Media / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
D016229:Amyloid beta-Peptides
Amyloid-β; Basement membranes; Cerebral amyloid angiopathy; Leptomeningeal arteries; Perivascular drainage