Cerebral amyloid angiopathy
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|Cerebral amyloid angiopathy|
|Classification and external resources|
Cerebral amyloid angiopathy (CAA), also known as congophilic angiopathy,1 is a form of angiopathy in which amyloid deposits form in the walls of the blood vessels of the central nervous system.2 The term congophilic is used because the presence of the abnormal aggregations of amyloid can be demonstrated by microscopic examination of brain tissue after application of a special stain called Congo red. The amyloid material is only found in the brain and as such the disease is not related to other forms of amyloidosis.
CAA has been identified as occurring either sporadically (generally in elderly populations)3 or in familial forms such as Flemish, Iowa, and Dutch types.456 Sporadic forms of CAA have been further characterized into two types based on deposition of amyloid β-protein (Aβ) in cortical capillaries.7 In all cases, it is defined by the deposition of Aβ in the leptomeningal and cerebral vessel walls.8
The reason for increased deposition of Aβ in sporadic CAA is still unclear with both increased production of the peptide9 and abnormal clearance having been proposed as potential causes.1011 Under normal physiology Aβ is cleared from the brain by four pathways: (1) endocytosis by astrocytes and microglial cells,12 (2) enzymatic degradation by neprilysin or insulysin10 (3) cleared by way of the blood brain barrier13 or (4) drained along periarterial spaces.11 Abnormalities in each of these identified clearance pathways have been linked to CAA.
In familial forms of CAA, the cause of Aβ build up is likely due to increased production rather than poor clearance.14 Mutations in the amyloid precursor protein (APP), Presenilin (PS) 1 and PS2 genes can result in increased rates of cleavage of the APP into Aβ.15
An immune mechanism has also been proposed.16
Amyloid deposition predisposes these blood vessels to failure, increasing the risk of a hemorrhagic stroke. Since this can be caused by the same amyloid protein that is associated with Alzheimer's dementia17 such brain hemorrhages are more common in people who suffer from Alzheimer's, however they can also occur in those who have no history of dementia. The hemorrhage within the brain is usually confined to a particular lobe and this is slightly different compared to brain hemorrhages which occur as a consequence of high blood pressure (hypertension) - a more common cause of a hemorrhagic stroke (or cerebral hemorrhage).
However, there are other types:
- the "Icelandic type" is associated with Cystatin C.22
- the "British type" is associated with ITM2B (also known as "BRI").23
Research is currently being conducted to determine if there is a link between cerebral amyloid angiopathy and ingestion of excessive quantities of aluminium, as occurred in the Camelford water pollution incident.24
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- Grabowski TJ, Cho HS, Vonsattel JP et al. (June 2001). "Novel amyloid precursor protein mutation in an Iowa family with dementia and severe cerebral amyloid angiopathy". Annals of Neurology 49 (6): 697–705. doi:10.1002/ana.1009. PMID 11409420.
- Maat-Schieman M, Roos R, van Duinen S. (December 2005). "Hereditary cerebral hemorrhage with amyloidosis-Dutch type". Neuropathology 25 (3): 288–297. doi:10.1111/j.1440-1789.2005.00631.x. PMID 16382777.
- Thal DR, Ghebremedhin E, Rüb U, Yamaguchi H, Del Tredici K, Braak H (March 2002). "Two Types of Sporadic Cerebral Amyloid Angiopathy". Journal of Neuropathology & Experimental Neurology 61 (3): 282–293. PMID 11895043.
- Glenner GG, Henry JH, Fujihara S. (1981). "Congophilic angiopathy in the pathogenesis of Alzheimer's degeneration". Annales de Pathologie 1 (2): 120–129. PMID 6169353.
- Li R, Lindholm K, Yang LB et al. (March 2004). "Amyloid β peptide load is correlated with increased β-secretase activity in sporadic Alzheimer's disease patients". Proceedings of the National Academy of Sciences of the United States of America 101 (1): 3632–3637. doi:10.1073/pnas.0205689101. PMC 373514. PMID 14978286.
- Iwata N, Tsubuki S, Takaki Y et al. (February 2000). "Identification of the major Abeta1–42-degrading catabolic pathway in brain parenchyma: suppression leads to biochemical and pathological deposition". Nature Medicine 6 (2): 143–150. doi:10.1038/72237. PMID 10655101.
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- Zlokovic BV (April 2005). "Neurovascular mechanisms of Alzheimer's neurodegeneration". Trends in Neurosciences 28 (4): 202–208. doi:10.1016/j.tins.2005.02.001. PMID 15808355.
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- Thal DR, Griffin WS, de Vos RA, Ghebremedhin E (June 2008). "Cerebral amyloid angiopathy and its relationship to Alzheimer's disease". Acta Neuropathol. 115 (6): 599–609. doi:10.1007/s00401-008-0366-2. PMID 18369648.
- Haacke EM, DelProposto ZS, Chaturvedi S et al. (February 2007). "Imaging cerebral amyloid angiopathy with susceptibility-weighted imaging". AJNR Am J Neuroradiol 28 (2): 316–7. PMID 17297004.
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- Chao CP, Kotsenas AL, Broderick DF (2006). "Cerebral amyloid angiopathy: CT and MR imaging findings". Radiographics 26 (5): 1517–31. doi:10.1148/rg.265055090. PMID 16973779.
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- "Government slammed for refusing to fund probe into death after one of worst water poisoning cases in British history". Daily Mail (London). 5 September 2008.