DECREASED LEVELS OF SOLUBLE AMYLOID BETA-PROTEIN PRECURSOR IN CEREBROSPINAL-FLUID OF LIVE ALZHEIMER-DISEASE PATIENTS

The amyloid beta-protein is deposited in senile plaques and the cerebr ovasculature in Alzheimer disease (AD). Since it is derived from prote olytic processing of its parent protein, the amyloid beta-protein prec ursor (APP), we investigated whether levels of the secreted forms of A PP are altered in cerebrospinal fluid (CSF) of AD patients. Quantitati ve immunoblotting studies with the anti-APP monoclonal antibody P2-1 r evealed that probable AD patients had markedly lower CSF APP levels th an did demented non-Alzheimer-type patients and healthy control subjec ts. Using antibody P2-1 in an enzyme-linked immunosorbent assay, we me asured CSF levels of APP in a larger population consisting of 13 patie nts diagnosed with probable AD, 18 patients diagnosed with dementia (n on-Alzheimer type), and 16 nondemented, healthy controls. Mean CSF lev els of APP were almost-equal-to 3.5-fold lower in the live patients di agnosed with probable AD compared to the demented non-Alzheimer-type c ontrols or the nondemented, healthy individuals. These findings sugges t that abnormal metabolism of APP is reflected in the extracellular fl uids of the central nervous system and that CSF levels of soluble APP provide a useful biochemical marker to assist in the clinical diagnosi s of AD.