Biochemical and immunocytochemical analyses were performed to evaluate the composition of the amyloid protein (A) deposited in the brains of patients with Alzheimer's disease (AD). To quantitate all As present, cerebral cortex was homogenized in 70% formic acid, and the supernatant was analyzed by sandwich enzyme-linked immunoabsorbent assays specific for various forms of A. In 9 of 27 AD brains examined, there was minimal congophilic angiopathy and virtually all A (96%) ended at A42(43). The other 18 AD brains contained increasing amounts of A ending at A40. From this set, 6 brains with substantial congophilic angiopathy were separately analyzed. In these brains, the amount of A ending at A42(43) was much the same as in brains with minimal congophilic angiopathy, but a large amount of A ending at A40 (76% of total A) was also present. Immunocytochemical analysis with monoclonal antibodies selective for As ending at A42(43) or A40 confirmed that, in brains with minimal congophilic angiopathy, virtually all A is A ending at A42(43) and showed that this A is deposited in senile plaques of all types. In the remaining AD brains, A42(43) was deposited in a similar fashion in plaques, but, in addition, widely varying amounts of A ending at A40 were deposited, primarily in blood vessel walls, where some A ending at A42(43) was also present. These observations indicate that As ending at A42(43), which are a minor component of the A in human cerebrospinal fluid and plasma, are critically important in AD where they deposit selectively in plaques of all kinds.

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