AMYLOID BETA-PROTEIN DEPOSITION IN THE LEPTOMENINGES AND CEREBRAL-CORTEX

To further investigate the process of amyloid beta-protein (A beta) de position, we determined, using sensitive enzyme immunoassays, the leve ls of A beta 40 and A beta 42 (A beta s) in the soluble and insoluble fractions of the leptomeninges (containing arachnoid mater and leptome ningeal vessels) and cerebral cortices from elderly control subjects s howing various stages of A beta deposition and from patients affected by Alzheimer's disease (AD). In both locations, insoluble A beta level s were higher by orders of magnitude than soluble A beta levels. Solub le A beta levels in cortices were much lower than those in leptomening es. In insoluble A beta in the cortex, A beta 42 was by far the predom inant species, and A beta 42 in AD cortices was characterized by the h ighest degree of modifications in the amino terminus. In contrast, thi s A beta 42 predominance was not observed in insoluble A beta in the l eptomeninges, which were found to be able to accumulate A beta s to an extent similar to that in the cortex, on a weight basis. The levels o f insoluble A beta in the leptomeninges or cortex generally correlated with the degree of cerebral amyloid angiopathy or the abundance of se nile plaque, respectively. However, the presence of plaque-free cortic al samples showing significant levels of insoluble A beta 42 suggests that biochemically detectable A beta accumulation precedes immunocytoc hemically detectable A beta deposition in the cortex.