Progress Review Cerebral Amyloid Angiopathy A Critical Review

Historical Perspective The clinicopathologic entity of cerebral congophilic or amyloid angiopathy (CAA) has been recognized since die early part of this century, though it has attained the 'limelight' over the past decade primarily for two reasons: 1) the observation that CAA is the probable cause of nontraumatic primary cerebral hemorrhage producing stroke in a significant proportion of patients, in particular those who are normotensive and elderly; and 2) its close association with the other microscopic hallmarks of Alzheimer's disease (AD), or senile dementia of the Alzheimer type (SDAT). Nevertheless, as with many other conditions that have been recently 'rediscovered,' elegant accounts and illustrations of the pathology of CAA appeared between 1900 and 1970'-" though interpretations of its significance and etiology were largely speculative in the absence of the modern molecular tools that have provided insights into its pathogenesis and reasonable hypotheses about its relation to brain aging. Unfortunately, it remains a puzzling entity, and CAA-related cerebral bleeding is likely to continue as a major clinical problem because of one simple fact: the single identifiable risk factor for the development of CAA—aging—is not as amenable to direct therapeutic intervention as other risk factors (e.g., hypertension) for various forms of stroke. The earlier terms used to describe CAA, "driisige Entartung der Arterien und Kapillaren," "angiopathie dyshorique," and congophilic angiopathy, nomenclature implying a specific etiology for the observed microangiopathy, now seem archaic though they retain descriptive value. Dyshoric angiopathy refers to amyloid in capillary walls often adjacent to senile plaques, whereas congophilic angiopathy describes amyloid in arterioles and small arteries. CAA or cerebrovascular amyloidosis (CVA) are synonyms currently used to describe all aspects of the microvascular change. The former will be used throughout this article, the purpose of which is to review the clinicopathologic features of CAA, emphasizing theories of pathogenesis and its importance as a cause of brain hemorrhage.