Superficial siderosis and amyloidosis

Abstract

Cerebral amyloid angiopathy (CAA), which results from amyloid deposition in the small and medium–sized blood vessels of the leptomeninges and central nervous system, is one of the cardinal causes of superficial siderosis (SS). Several amyloid precursor proteins are known to cause CAA. Aβ type CAA is the most frequently found in elderly people or patients with Alzheimer's disease (AD). Cystatin C, prion protein, ABri/ADan, transthyretin (TTR), and gelsolin, are all associated with hereditary CAA. Hereditary ATTR (ATTRv) amyloidosis is an autosomal dominant disease caused by mutations in TTR gene. In several specific TTR mutations including L12P, D18G, A25T, V30G, A36P, T49P, G53E, G53A, G53R, F64S, T69H, and Y114C, leptomeningeal vessels are severely involved by amyloid deposits. On the other hand, in TTR V30M, which is the most common variant type in Japanese hereditary ATTR amyloidosis, CAA was not so noticeable except for homozygous V30M patients. However, with improvement of the prognosis by liver transplantation or disease modifying drugs, CAA has recently become a major problem even in heterozygous V30M patients. These patients developed transient ischemic attack (TIA)–like episodes, stroke, and intracranial hemorrhages, causing SS.