Disease relevance of Cerebral Amyloid Angiopathy

• Intracranial hemorrhage: cerebral amyloid angiopathy or nasal decongestants [1]?
• Accumulating data suggest involvement of cystatin C in the pathogenic processes leading to amyloid deposition in cerebral vasculature and most significantly to cerebral hemorrhage in patients with cerebral amyloid angiopathy (CAA) [2].
• Spatial clustering of hemorrhages in probable cerebral amyloid angiopathy [3].
• INTERPRETATION: Leukoencephalopathy, ischemic infarcts, microbleeds, and macrobleeds are indicative of an underlying microangiopathy, of which the best-known causes are hypertension, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, and cerebral amyloid angiopathy [4].
• These include Alzheimer's disease, Down syndrome, and sporadic and hereditary cerebral amyloid angiopathies (CAAs) related to mutations within the Abeta sequence [5].

Psychiatry related information on Cerebral Amyloid Angiopathy

• The E693Q mutation in the amyloid beta precursor protein (APP) leads to cerebral amyloid angiopathy (CAA), with recurrent cerebral hemorrhagic strokes and dementia [6].
• The protein component of Alzheimer's disease amyloid [neurofibrillary tangles (NFT), amyloid plaque core and congophilic angiopathy] is an aggregated polypeptide with a subunit mass of 4 kd (the A4 monomer) [7].
• The acceptability of presymptomatic testing in 21 people at 50% risk for the APP-692 mutation causing presenile Alzheimer's disease or cerebral haemorrhage resulting from cerebral amyloid angiopathy (FAD-CH), and in 43 people at 50% risk for hereditary Pick disease (HPD) was assessed [8].
• Creutzfeldt-Jakob disease and cerebral amyloid angiopathy [9].
• Many forms of vascular dementia have been described: multi-infarct dementia, lacunar dementia, Binswanger's subcortical encephalopathy, cerebral amyloid angiopathy, white matter lesions associated with dementias, single infarct dementia, dementia linked to hypoperfusion and haemorrhagic dementia [10].

High impact information on Cerebral Amyloid Angiopathy

• APP locus duplication causes autosomal dominant early-onset Alzheimer disease with cerebral amyloid angiopathy [11].
• More TGF-beta1 messenger RNA was present in post-mortem brain tissue of Alzheimer's patients than in controls, the levels correlating strongly with amyloid-beta deposition in the damaged cerebral blood vessels of patients with cerebral amyloid angiopathy [12].
• Mutations in AbetaPP cause deposition of Abeta amyloid fibrils in brain parenchyma and cerebral vessels, resulting in Alzheimer's disease (AD) and/or cerebral amyloid angiopathy (CAA) [13].
• We examined the potential role of the extra-cellular matrix-degrading enzyme, matrix metalloproteinase-9 (MMP-9), in the pathogenesis of cerebral amyloid angiopathy (CAA)-induced spontaneous hemorrhage [14].
• Neuropathological examination of the proband revealed severe cerebral amyloid angiopathy, widespread neurofibrillary tangles, and unusually extensive distribution of Abeta40 in plaques [15].

Chemical compound and disease context of Cerebral Amyloid Angiopathy

• Immunohistochemical study of cerebral amyloid angiopathy. II. Enhancement of immunostaining using formic acid pretreatment of tissue sections [16].
• The sections were stained by the Congo-red method and examined under polarized light for the presence of cortical (parenchymal) cerebral amyloid angiopathy (CAA) [17].
• Plaque and dyshoric amyloid exhibited variable sensitivity to permanganate oxidation; Congophilic angiopathy was resistant to oxidation [18].
• The non-amyloid beta component of Alzheimer's disease amyloid (NAC) is detected in cerebral amyloid angiopathy; and the precursor of NAC is now known to be identical to alpha-synuclein (alpha-S), a major component of Lewy bodies in Parkinson's disease [19].
• Initiating an antihypertensive regimen in a patient with nonlobar microbleeds suggestive of hypertensive vasculopathy, and withholding warfarin in patients with lobar microbleeds suggestive of cerebral amyloid angiopathy, are emerging prevention strategies [20].

Biological context of Cerebral Amyloid Angiopathy

• The binary nature of the EI involving Lys-28 provides a mechanistic explanation for the linkage of amino acid substitutions at Glu-22 with Alzheimer's disease and cerebral amyloid angiopathy [21].
• The presence of the diagnostic point mutation makes HCHWA-D a useful model to study the effects of cerebral amyloid angiopathy in vivo [22].
• The incidence of cerebral amyloid angiopathy did not correlate with blood pressure or with the severity of cerebral atherosclerosis [23].
• Familial AD displays genetic and phenotypic heterogeneity, meaning that mutations of different genes may cause the AD phenotype, and that different mutations of the same gene may cause phenotypically distinct disorders, including Alzheimer-type dementia and cerebral amyloid angiopathy with cerebral hemorrhages and stroke [24].
• OBJECTIVE: In view of the association of the apolipoprotein E (APOE) epsilon 4 allele with poor outcome after traumatic brain injury we determined the frequency of cerebral amyloid angiopathy (CAA) and the extent of haemorrhagic pathology in relation to APOE genotype in an autopsy series of 88 head injured cases [25].

Anatomical context of Cerebral Amyloid Angiopathy

• These results indicate that (1) the A beta species initially deposited in the brain as senile plaques is A beta 42(43) and A beta 40 only appears a decade later, and (2) in cerebral amyloid angiopathy A beta 40 appears as early as A beta 42(43) [26].
• We suspected cystatin C-type cerebral amyloid angiopathy because of the low level of cystatin C in the cerebrospinal fluid [27].
• Giant cell arteritis in association with cerebral amyloid angiopathy: immunohistochemical and molecular studies [28].
• Degeneration of vascular muscle cells in cerebral amyloid angiopathy of Alzheimer disease [29].
• Spinal cord vascular and leptomeningeal amyloid beta-protein deposition in a case with cerebral amyloid angiopathy [30].

Gene context of Cerebral Amyloid Angiopathy

• Here, we describe significant deposition of amyloid beta (Abeta) in the cerebral vasculature [cerebral amyloid angiopathy (CAA)] in aging APP23 mice that had striking similarities to that observed in human aging and Alzheimer's disease [31].
• These data demonstrate that ApoE facilitates the formation of both neuritic and cerebrovascular plaques, which are pathological hallmarks of AD and cerebral amyloid angiopathy [32].
• Neuronal and glial ApoE4 promoted cerebral amyloid angiopathy as extensively as mutant PS1 but with pronounced regional differences: cortical angiopathy was induced by neuronal ApoE4 while thalamic angiopathy was again independent of ApoE4 source [33].
• Novel presenilin-1 mutation with widespread cortical amyloid deposition but limited cerebral amyloid angiopathy [34].
• Genetic-morphologic association study: association between the low density lipoprotein-receptor related protein (LRP) and cerebral amyloid angiopathy [35].

Analytical, diagnostic and therapeutic context of Cerebral Amyloid Angiopathy

• We describe a sporadic case of leukoencephalopathy with cystatin C-type cerebral amyloid angiopathy diagnosed during life by enzyme-linked immunosorbent assay [27].
• A cytochemical study of 14 cases of adult dementia revealed the presence of gamma globulin in the amyloid of three cases of congophilic angiopathy by means of immunofluorescence microscopy [36].
• Our studies suggest that A beta, irrespective of its origin within vascular myocytes or brain parenchyma, is responsible not only for cerebral amyloid angiopathy, but also for the degeneration of the cerebral microvasculature, which may profoundly affect brain perfusion and BBB functions [37].
• In this review, the clinical spectrum of cerebral amyloid angiopathy will be described, based on retrospective studies from the literature [38].
• Passive immunization with an antibody directed against the N terminus of amyloid beta (Abeta) has recently been reported to exacerbate cerebral amyloid angiopathy (CAA)-related microhemorrhage in a transgenic animal model [39].

References