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.