Transthyretin-type cerebral amyloid angiopathy in type I familial amyloid polyneuropathy

To clarify the pathogenesis of cerebrovascular amyloid deposits, histological and immunocytochemical studies were performed on the central nervous system (CNS) in ten cases with type I familial amyloid polyneuropathy (FAP). They commonly suffered from peripheral somatic and autonomic nerve disorders without any CNS dysfunctions. However, all cases showed CNS amyloid deposits, mainly on the leptomeningeal vessels and pia-arachnoid membranes, with arteries and arterioles in the subarachnoidal space being the predominant site of cerebral amyloid accumulation. Using immunocytochemical staining methods with antibodies to amyloid beta-protein, human cystatin C and transthyretin (prealbumin), all of these amyloid deposits were specifically immunolabeled by the anti-human transthyretin antibody. However, there was no transthyretin-related amyloid deposits in the brain parenchyma. It is concluded that CNS transthyretin-immunoreactive amyloid deposition with cerebral amyloid angiopathy (CAA) is a common pathological finding in this disease. Moreover, the patients with type I FAP are known to have an amyloid protein precursor (a variant of transthyretin) in serum. This transthyretin type of CAA, therefore, seems to be an example of cerebrovascular amyloid deposits derived from a serum precursor.