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

Deposition of amyloid-beta in the walls of human leptomeningeal arteries in relation to perivascular drainage pathways in cerebral amyloid angiopathy
Deposition of amyloid-beta in the walls of human leptomeningeal arteries in relation to perivascular drainage pathways in cerebral amyloid angiopathy
Deposition of amyloid beta (AB) in the walls of cerebral arteries as cerebral amyloid angiopathy (CAA) suggests an age-related failure of perivascular drainage of soluble A? 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 A? accumulates in artery walls. Paraffin sections of post-mortem human occipital cortex were immunostained for collagen IV, fibronectin, nidogen 2, AB 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: AB 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 AB. The pattern of development of CAA in the human brain suggests expansion of AB 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 AB 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.
0925-4439
1037-1046
Keable, Abby
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Fenna, Kate
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Yuen, Ho Ming
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Johnston, David A.
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Smyth, Neil R.
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Smith, Colin
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Al-Shahi Salman, Rustam
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Samarasekera, Neshika
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Nicoll, James A.R.
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Attems, Johannes
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Kalaria, Rajesh N.
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Weller, Roy O.
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Carare, Roxana-Octavia
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Keable, Abby
175d97e8-3baf-4130-94a8-f981810e2c96
Fenna, Kate
e29f7006-aa37-447d-ae52-40caedf4ff5a
Yuen, Ho Ming
b1df4c57-0c2a-44ac-ab40-22b88e8effe8
Johnston, David A.
b41163c9-b9d2-425c-af99-2a357204014e
Smyth, Neil R.
0eba2a40-3b43-4d40-bb64-621bd7e9d505
Smith, Colin
d991039c-1c8b-4aff-a306-b45c67c486e9
Al-Shahi Salman, Rustam
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Samarasekera, Neshika
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Nicoll, James A.R.
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Attems, Johannes
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Kalaria, Rajesh N.
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Weller, Roy O.
4a501831-e38a-4d39-a125-d7141d6c667b
Carare, Roxana-Octavia
0478c197-b0c1-4206-acae-54e88c8f21fa

Keable, Abby, Fenna, Kate, Yuen, Ho Ming, Johnston, David A., Smyth, Neil R., Smith, Colin, Al-Shahi Salman, Rustam, Samarasekera, Neshika, Nicoll, James A.R., Attems, Johannes, Kalaria, Rajesh N., Weller, Roy O. and Carare, Roxana-Octavia (2016) Deposition of amyloid-beta in the walls of human leptomeningeal arteries in relation to perivascular drainage pathways in cerebral amyloid angiopathy. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1862 (5), 1037-1046. (doi:10.1016/j.bbadis.2015.08.024). (PMID:26327684)

Record type: Article

Abstract

Deposition of amyloid beta (AB) in the walls of cerebral arteries as cerebral amyloid angiopathy (CAA) suggests an age-related failure of perivascular drainage of soluble A? 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 A? accumulates in artery walls. Paraffin sections of post-mortem human occipital cortex were immunostained for collagen IV, fibronectin, nidogen 2, AB 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: AB 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 AB. The pattern of development of CAA in the human brain suggests expansion of AB 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 AB 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.

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Accepted/In Press date: 26 August 2015
e-pub ahead of print date: 29 August 2015
Published date: May 2016
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 394796
URI: https://eprints.soton.ac.uk/id/eprint/394796
ISSN: 0925-4439
PURE UUID: 8ca74de9-46b6-43b1-9c9d-aa1732b49e13
ORCID for David A. Johnston: ORCID iD orcid.org/0000-0001-6703-6014
ORCID for James A.R. Nicoll: ORCID iD orcid.org/0000-0002-9444-7246

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Date deposited: 24 May 2016 10:19
Last modified: 10 Dec 2019 01:47

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