BIOCHEMICAL AND MOLECULAR GENETIC STUDY ON THE PATHOGENESIS OF CEREBRAL AMYLOID ANGIOPATHY

1992 Fiscal Year Final Research Report Summary

• Project/Area Number: 02807083
• Research Category: Grant-in-Aid for General Scientific Research (C)
• Allocation Type: Single-year Grants
• Research Field: Neurology
• Research Institution: SHINSHU UNIVERSITY SCHOOL OF MEDICINE
• Principal Investigator: YANAGISAWA Nobuo SHINSHU UNIVERSITY SCHOOL OF MEDICINE THIRD DEPARTMENT OF INTERNAL MEDICINE PROFESSOR, 医学部, 教授 (00010025)
• Co-Investigator(Kenkyū-buntansha): IKEDA Shu-ichi SHINSHU UNIVERSITY SCHOOL OF MEDICINE THIRD DEPARTMENT OF INTERNAL MEDICINE ASSO, 医学部, 講師 (60135134)
• Project Period (FY): 1990 – 1992
• Keywords: Cerebral Amyloid Angiopathy / Amyloid / beta-protein / Cystatin C / Transthyretin

Research Abstract

Cerebral amyloid angiopathy (CAA) is characterized by amyloid deposition within the walls of leptomeningeal and cortical blood vessels. To clarify the pathogenesis of this pathological condition, histological and immunocytochemical studies were performed on the central nervous system in 10 cases with familial amyloid polyneuropathy (FAP). FAP is a systemic amyloidosis and it is well known that a variant tranthyretin with a methionine for valine substitution at position 30 is present in the serum of patients with this disorder as an amyloid precursor. All cases showed transthyretin-immunoreactive amyloid deposits, mainly on the leptomeningeal vessels and pia-arachnoid membranes. The complete sequence analysis of this amyloid fibril protein isolated from the meningeal vessels of a patient revealed the same biochemical feature as that of serum variant transthyretin. These findings suggest that cerebrovascular amyloid fibril protein in FAP derive from a serum precursor. On the other hand, it has been noted that CAA seen in some sporadic aged individuals can show a dual immunohistochemical reactivity towards antibodies to both beta-protein ancystatin C. We isolated and carried out a chemical analysis of the amyloid fibril protein from the leptomeningeal vessels of a case with this disorder. A crude amyloid fibril fraction reacted only with anti-beta-protein antibody, and cystatin C immunoreacitivity was observed in the first PBS supernatant. Complete amino acid sequence of this cystatin C-immunoreactive protein showed a homologous structure to that of normal cystatin C. It is concluded that cystatin C is not an intrinsic component of the amyloid fibril in this type of CAA.