Amyloid β-proteins 1—40 and 1—42(43) in the soluble fraction of extra- and intracranial blood vessels

To investigate the process of amyloid β-protein (Aβ) accumulation in cerebral amyloid angiopathy (CAA), the levels of Aβ were determined in the soluble fraction of extra- and intracranial blood vessels and leptomeninges obtained at autopsy. Two enzyme immunoassays were employed that are known to sensitively and specifically quantify two Aβ species, Aβ1–40 and 1–42(43). Aβ was detectable in the intracranial blood vessels and leptomeninges with the latter containing the highest levels, while it was undetectable in the extracranial blood vessels. Thus the levels of soluble Aβ correlated well with the prediiection sites for CAA. Among individuals aged 20 to 90, the Aβ levels in the leptomeninges increased sharply in those aged 50 to 70 and thereafter tended to decline. However, only slight degrees of CAA were detected by immunocytochemistry, even when those leptomeninges contained high levels of Aβ comparable with those in Alzheimer's disease. The level of Aβ1–42 was almost always severalfold that of Aβ1–40 in the soluble fraction of leptomeninges. This is in good agreement with the immunocytochemical result showing the presence of Aβ40-negative, Aβ42(43)-positive meningeal vessels. These results indicate that Aβ1–42 is the initially deposited species in CAA and that the disruption of Aβ homeostasis precedes Aβ deposition in the meningeal vessels.