[Cerebral amyloid angiopathy with familial transthyretin-derived oculoleptomeningeal amyloidosis].

Cerebral amyloid angiopathy (CAA) is caused by the accumulation of amyloid fibrils on vascular walls and is a well-known cause of cerebral hemorrhages in the elderly. This disease manifests as recurrent or multiple simultaneous subcortical hematomas, occasionally leading to fatal hemorrhages. Additionally, it is noteworthy that CAA-related hemorrhages can develop in individuals aged around 50 years. Although a few different amyloid fibril proteins have been isolated from patients with CAA, the most common protein is Aβ, which is also the main component of senile plaques in Alzheimer's disease. Recent studies have suggested that corticosteroid therapy is effective for preventing the recurrence of CAA-related hemorrhages. Hereditary generalized amyloidosis usually manifests as familial amyloid polyneuropathy (FAP), showing severe involvement of peripheral somatic and autonomic nerves. Many variant forms of transthyretin (TTR) with a single amino acid substitution have been identified as causative amyloid precursor proteins in FAP. Moreover, a small number of TTR gene mutations causes a rare phenotype of systemic amyloidosis characterized by preferential deposition of TTR-derived amyloid proteins in the vitreous body in the eye, as well as the leptomeninges and subarachnoidal vessels in the central nervous system (CNS). This disorder is called familial oculoleptomeningeal or leptomeningeal amyloidosis and is characterized clinically by CNS symptoms, including progressive dementia, seizures, ataxia, spastic paresis, and stroke-like episodes. Since the variant forms of TTR in this amyloidosis are derived from the retinal epithelium or choroid plexus, liver transplantation-an effective treatment for FAP-is considered less effective for treating this rare form of TTR-related systemic amyloidosis.