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.

https://www.ahajournals.org/doi/pdf/10.1161/01.STR.18.2.311

Cerebral amyloid angiopathy. A critical review.

The Nomenclature Committee of the International Society of Amyloidosis (ISA) met during the XVth Symposium of the Society, 3 July–7 July 2016, Uppsala, Sweden, to assess and formulate recommendatio...

https://www.tandfonline.com/doi/pdf/10.1080/13506129.2016.1257986

Amyloid fibril proteins and amyloidosis: chemical identification and clinical classification International Society of Amyloidosis 2016 Nomenclature Guidelines.

The Nomenclature Committee of the International Society of Amyloidosis (ISA) met during the XIVth Symposium of the Society, April 27–May 1, 2014, Indianapolis, IN, to assess and formulate recommend...

Nomenclature 2014: Amyloid fibril proteins and clinical classification of the amyloidosis

Natural History of Wild-Type Transthyretin Cardiac Amyloidosis and Risk Stratification Using a Novel Staging System

https://www.amjmed.com/article/0002-9343(83)90443-6/pdf

Frequency and distribution of senile cardiovascular amyloid: A clinicopathologic correlation

Senile systemic amyloid contains the prealbumin-like fibril protein, ASc1, and is the only known form of systemic age-related amyloid. Although it involves predominantly the heart, it may be found in a wide range of tissues. Immunologic studies show that ASc1 cross reacts with human prealbumin (PA) in binding reactions but not in immunoprecipitation reactions. Protein ASc1 shows complete homology with PA in four residues isolated. However, unlike PA, Asc1 may have a blocked N-terminus and is composed of at least three components. Anti-ASc1 forms a line of precipitation with sera from patients with familial amyloidosis. A similar weak reaction has been observed in some elderly patients with senile systemic amyloid.

Senile systemic amyloidosis.

Amyloid deposits were found subepithelially in the seminal vesicles of 34 of 209 consecutively studied men. The incidence increased with age and was found in 21% of men over 75 years. This senile seminal vesicle amyloidosis (SSVA) is a localized disorder, and the amyloid substance has unique histochemical and immunochemical properties not shared with any other amyloid described until now.

Amyloid of the seminal vesicles. A distinctive and common localized form of senile amyloidosis.

Serum prealbumin and retinol-binding protein in the prealbumin-related senile and familial forms of systemic amyloidosis.

Aortic tissues from 22 elderly patients were analyzed by Congo red staining for amyloid deposits. All samples contained amyloid, which was resistant to the potassium permanganate reaction. Tryptophan was present in all amyloid deposits. The amyloid failed to react with antiserums to amyloid fibril protein ASc1 or human prealbumin, proteins previous demonstrated in generalized senile cardiac amyloid. It also differed from age-related isolated atrial amyloid, which has been shown to lack tryptophan. Deposits did not react with antiserums specific for amyloid fibril proteins of the A lambda IV, A lambda VI, AA, or AEt types. These results indicate that senile aortic amyloid is distinct from amyloid present in primary and secondary amyloidosis and appears to represent a third form of cardiovascular amyloid associated with the aging process.

Pitkänen P

Papers

Senile systemic amyloidosis.

Amyloid of the seminal vesicles. A distinctive and common localized form of senile amyloidosis.

Serum prealbumin and retinol-binding protein in the prealbumin-related senile and familial forms of systemic amyloidosis.

Senile aortic amyloid. A third distinctive type of age-related cardiovascular amyloid.