Alzheimer's disease amyloid precursor protein is present in senile plaques and cerebrospinal fluid: immunohistochemical and biochemical characterization.

The amyloid fibrils deposited in cerebral vessel walls and senile plaques in Alzheimer's disease are polymeric forms of a 4 kDa fragment produced by proteolysis of a putative precursor protein (APP). Using antibodies to several fragments of the deduced precursor, we were able to demonstrate the presence of APP in senile plaques, brain extracts and cerebrospinal fluid. Membrane-associated APP is detected as a group of 105-135 kDa proteins while soluble APP is predominantly 105 kDa, does not react with an anti C-terminal antibody, and is 10 kDa shorter than the membrane-bound APP. Amino terminal sequence of the tissue 105 kDa protein indicates that APP begins at residue 18 of the cDNA sequence. These findings imply that i) two forms of APP are detected: membrane-bound and secreted, and ii) APP can be processed in situ.