Amyloid β‐protein deposition in the leptomeninges and cerebral cortex

To further investigate the process of amyloid β‐protein (Aß) deposition, we determined, using sensitive enzyme immunoassays, the levels of Aβ40 and Aβ42 (Aβs) in the soluble and insoluble fractions of the leptomeninges (containing arachnoid mater and leptomeningeal vessels) and cerebral cortices from elderly control subjects showing various stages of Aβ deposition and from patients affected by Alzheimer's disease (AD). In both locations, insoluble Aβ levels were higher by ordersof magnitude than soluble Aβ levels. Soluble Aβ levels. Soluble Aβ levels in cortices were much lower than those in leptomeninges. In insoluble Aβ in the cortex, Aβ42 was by far the predominant species, and Aβ42 in AD cortices was characterized by the highest degree of modifications in the amino terminus. In contrast, this Aβ42 predominance was not observed in insoluble Aβ in the leptomenings, which were found to be able to accumulate Aβs to an extent similar to that in the cortex, on a weight basis. The levels of insoluble Aβ in the leptomeninges or cortex generally correlated with the degree of cerebral amyloid angiopathy or the abundance of senile plaque, respectively. However, the presence of plaque‐free cortical samples showing significant levels of insoluble Aβ42 suggests that biochemically detectable Aβ accumulation precedes immunocytochemically detectable Aβ deposition in the cortex.