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

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1862

Article

Keable, Abby¹  Fenna, Kate¹  Yuen, Ho Ming¹  Johnston, David A.¹  Smyth, Neil R.¹  Smith, Colin²  Salman, Rustam Al-Shahi²  Samarasekera, Neshika²  Nicoll, James A. R.¹  Attems, Johannes³  Kalaria, Rajesh N.³  Weller, Roy O.¹  Carare, Roxana O.¹ 

[1] Univ Southampton, Fac Med, Tremona Rd, Southampton SO16 6YD, Hants, England

[2] Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh EH8 9YL, Midlothian, Scotland

[3] Newcastle Univ, Inst Neurosci, Campus Ageing & Vital, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England

关键词: Amyloid-beta;    Leptomeningeal arteries;    Perivascular drainage;    Basement membranes;    Cerebral amyloid angiopathy;   

DOI  :  10.1016/j.bbadis.2015.08.024

来源: Elsevier

【 摘 要 】

Deposition of amyloid beta (A beta) in the walls of cerebral arteries as cerebral amyloid angiopathy (CAA) suggests an age-related failure of perivascular drainage of soluble A beta 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 beta accumulates in artery walls. Paraffin sections of post-mortem human occipital cortex were immunostained for collagen IV, fibronectin, nidogen 2, A beta 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: A beta 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 A beta. The pattern of development of CAA in the human brain suggests expansion of AS 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 A beta 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. (c) 2015 The Authors. Published by Elsevier B.V.

【 授权许可】

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