Insights into the pathogenesis and pathogenicity of cerebral amyloid angiopathy

被引:56
作者
Love, Seth [1 ]
Miners, Scott [1 ]
Palmer, Jen [1 ]
Chalmers, Katy [1 ]
Kehoe, Patrick [1 ]
机构
[1] Univ Bristol, Frenchay Hosp, Inst Clin Neurosci, Dept Neuropathol,Dementia Res Grp, Bristol BS16 1LE, Avon, England
来源
FRONTIERS IN BIOSCIENCE-LANDMARK | 2009年 / 14卷
关键词
Cerebral Amyloid Angiopathy; Alzheimer's Disease; Amyloid beta Peptide; Apolipoprotein E; Neprilysin; Endothelin-Converting Enzyme; Insulin-Degrading Enzyme; Angiotensin-Converting Enzyme; Plasmin; Transforming Growth Factor beta 1; Extracellular Matrix; APOLIPOPROTEIN-E GENOTYPE; ANGIOTENSIN-CONVERTING ENZYME; BLOOD-BRAIN-BARRIER; E-EPSILON; 4; ALZHEIMERS-DISEASE BRAIN; FLUID DRAINAGE PATHWAYS; ANEURYSMAL SUBARACHNOID HEMORRHAGE; INSULIN-DEGRADING ENZYME; CENTRAL-NERVOUS-SYSTEM; SMOOTH-MUSCLE-CELLS;
D O I
10.2741/3567
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Amyloid-beta (Abeta) cerebral amyloid angiopathy (CAA) affects most Alzheimer's disease (AD) patients and similar to 30% of otherwise-normal elderly people. APOE epsilon 4 is a major risk factor for CAA in AD. Neurons are probably the source of the vascular Abeta. CAA develops when Abeta is deposited in the vessel walls along or across which it normally passes into the CSF and bloodstream. Vascular deposition is facilitated by factors that increase Abeta40: Abeta42, impede perivascular passage of Abeta or raise its concentration. The levels of some Abeta-degrading enzymes are reduced in AD patients with CAA. However, angiotensin-converting enzyme activity is increased and may act via angiotensin II to increase transforming growth factor beta1, a potent inducer of ECM synthesis. CAA is a cause of intracerebral haemorrhage and cerebral ischaemic damage. In AD, neuritic degeneration is accentuated around Abeta-laden vessels. Rarely, CAA is associated with angiitis. The balance between parenchymal and cerebrovascular degradation of Abeta, and regulation of perivascular extracellular matrix production, are likely to be key determinants of Abeta distribution and pathogenicity within the brain.
引用
收藏
页码:4778 / 4792
页数:15
相关论文
共 135 条
[11]   Mechanisms of cerebrovascular amyloid deposition - Lessons from mouse models [J].
Burgermeister, P ;
Calhoun, ME ;
Winkler, DT ;
Jucker, M .
VASCULAR FACTORS IN ALZHEIMER'S DISEASE, 2000, 903 :307-316
[12]   Phenotype associated with APP duplication in five families [J].
Cabrejo, Lucie ;
Guyant-Marechal, Lucie ;
Laquerriere, Annie ;
Vercelletto, Martine ;
De la Fourniere, Francois ;
Thomas-Anterion, Catherine ;
Verny, Christophe ;
Letournel, Franck ;
Pasquier, Florence ;
Vital, Anne ;
Checler, Frederic ;
Frebourg, Thierry ;
Campion, Dominique ;
Hannequin, Didier .
BRAIN, 2006, 129 :2966-2976
[13]   Cerebral beta amyloid angiopathy is a risk factor for cerebral ischemic infarction. A case control study in human brain biopsies [J].
Cadavid, D ;
Mena, E ;
Koeller, K ;
Frommelt, RA .
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 2000, 59 (09) :768-773
[14]  
Carare-Nnadi R, 2006, NEUROPATH APPL NEURO, V32, P223
[15]   Declining expression of neprilysin in Alzheimer disease vasculature: Possible involvement in cerebral amyloid angiopathy [J].
Carpentier, M ;
Robitaille, Y ;
DesGroseillers, L ;
Boileau, G ;
Marcinkiewicz, M .
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 2002, 61 (10) :849-856
[16]   Contributors to white matter damage in the frontal lobe in Alzheimer's disease [J].
Chalmers, K ;
Wilcock, G ;
Love, S .
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, 2005, 31 (06) :623-631
[17]   APOE ε4 influences the pathological phenotype of Alzheimer's disease by favouring cerebrovascular over parenchymal accumulation of Aβ protein [J].
Chalmers, K ;
Wilcock, GK ;
Love, S .
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, 2003, 29 (03) :231-238
[18]   APOE promoter, ACE1 and CYP46 polymorphisms and β-amyloid in Alzheimer's disease [J].
Chalmers, KA ;
Culpan, D ;
Kehoe, PG ;
Wilcock, GK ;
Hughes, A ;
Love, S .
NEUROREPORT, 2004, 15 (01) :95-98
[19]   TRANSFORMING GROWTH-FACTOR-BETA IN ALZHEIMERS-DISEASE [J].
CHAO, CC ;
HU, SX ;
FREY, WH ;
ALA, TA ;
TOURTELLOTTE, WW ;
PETERSON, PK .
CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY, 1994, 1 (01) :109-110
[20]   Genetic-morphologic association study: association between the low density lipoprotein-receptor related protein (LRP) and cerebral amyloid angiopathy [J].
Christoforidis, M ;
Schober, R ;
Krohn, K .
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, 2005, 31 (01) :11-19