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Advances in our Understanding of the Pathophysiology, Detection and Management of Cerebral Amyloid Angiopathy

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Published Online: May 15th 2012 European Neurological Review, 2012;7(2):134-9 DOI:
Authors: Octavio M Pontes-Neto, Eitan Auriel, Steven M Greenberg
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Cerebral amyloid angiopathy (CAA) is pathologically defined as the deposition of amyloid protein, most commonly the amyloid β peptide (Aβ), primarily within the media and adventitia of small and medium-sized arteries of the leptomeninges, cerebral and cerebellar cortex. This deposition likely reflects an imbalance between Aβ production and clearance within the brain and leads to weakening of the overall structure of brain small vessels, predisposing patients tolobar intracerebral haemorrhage (ICH), brain ischaemia and cognitive decline. CAA is associated with markers of small vessel disease, like lobar microbleeds and white matter hyperintensities on magnetic resonance imaging. Therefore, it can be now be diagnosed during life with reasonable accuracy by clinical and neuroimaging criteria. Despite the lack of a specific treatment for this condition, the detection of CAA may help in the management of patients, regarding the prevention of major haemorrhagic complications and genetic counselling. This review discusses recent advances in our understanding of the pathophysiology, detection and management of CAA.


Amyloid angiopathy, intracerebral haemorrhage, cognitive decline, stroke, amyloid


Cerebral amyloid angiopathy (CAA) is a disorder of the central nervous system characterised by the deposition of amyloid proteins in the wall of small- to medium-sized vessels, most frequently arteries, within the leptomeninges and cortex of the brain.1 In vessels affected by CAA, local muscle and elastic elements of the arterial wall are lost and replaced by amyloid fibrils, primarily the amyloid-β (Aβ) peptide. Since the first description of neurovascular amyloid deposition in 1909 by Gustav Oppenheim, sound scientific evidence has supported the concept that the associated disruption of the overall structure of those small vessels predisposes to both ischaemic small vesseldisease and cerebral haemorrhage.2–4

Sporadic CAA is a major cause of lobar intracerebral haemorrhage (ICH) and cognitive decline in the elderly, including the normotensive population.5,6 Hereditary forms of CAA are generally rare, usually more severe and earlier in onset. Rare non-Aβ familial CAAs can also present clinically with lobar ICH.7 Regarding sporadic CAA, two major challenges persist:

  • a definitive diagnosis requires a neuropathological exam; and8
  • no treatment or preventive strategy for CAA or CAA-ICH has been firmly established.

Nevertheless, in the last decades of research, there has been remarkable progress in our understanding of this condition. CAA pathology has been associated with markers of small vessel disease, including lobar cerebral microbleeds (CMB) and white matter hyperintensities on magnetic resonance imaging (MRI).9–11 The availability of MRI sequences that are particularly sensitive to susceptibility effects like the T2* gradient-recalled echo (GRE) and susceptibility weighted imaging (SWI) now allow reliable assessment of an individual’s haemorrhagic burden over time and reasonable accuracy by clinical and neuroimaging diagnostic criteria.10–13 As our understanding of CAA pathophysiology evolves, specific targets have been identified as candidates for the prevention and treatment of this condition.14 As newresearch tools such as the Pittsburgh Compound B (PiB) or other amyloid-imaging agents for positron emission tomography (PET) scan become incorporated into clinical practice, it may also be possible to detect vascular amyloid deposition in the brain noninvasively in living patients, perhaps before an ICH or significant cognitive decline.15

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Article Information:

The authors have no conflicts of interest to declare.


Steven M Greenberg, J Philip Kistler Stroke Research Center, Massachusetts General Hospital, 175 Cambridge Street, Suite 300, Boston, MA 02114, US. E:


The authors would like to thank Matthew P Frosch, Andrew Dumas, Edip Gurol and Alison Ayres for their help with the pictures of this manuscript. Octavio M Pontes-Neto receives research support from the Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP).




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