title: Decreased levels of soluble amyloid beta-protein precursor in cerebrospinal fluid of live Alzheimer disease patients.
abstract: The amyloid beta-protein is deposited in senile plaques and the cerebrovasculature in Alzheimer disease (AD). Since it is derived from proteolytic processing of its parent protein, the amyloid beta-protein precursor (APP), we investigated whether levels of the secreted forms of APP are altered in cerebrospinal fluid (CSF) of AD patients. Quantitative immunoblotting studies with the anti-APP monoclonal antibody P2-1 revealed that probable AD patients had markedly lower CSF APP levels than did demented non-Alzheimer-type patients and healthy control subjects. Using antibody P2-1 in an enzyme-linked immunosorbent assay, we measured CSF levels of APP in a larger population consisting of 13 patients diagnosed with probable AD, 18 patients diagnosed with dementia (non-Alzheimer type), and 16 nondemented, healthy controls. Mean CSF levels of APP were approximately 3.5-fold lower in the live patients diagnosed with probable AD compared to the demented non-Alzheimer-type controls or the nondemented, healthy individuals. These findings suggest that abnormal metabolism of APP is reflected in the extracellular fluids of the central nervous system and that CSF levels of soluble APP provide a useful biochemical marker to assist in the clinical diagnosis of AD.
authors.affiliation: Department of Microbiology and Molecular Genetics, University of California, Irvine 92717.
authors.forename: W E
authors.initials: WE
authors.lastname: Van Nostrand
authors.forename: S L
authors.initials: SL
authors.lastname: Wagner
authors.forename: W R
authors.initials: WR
authors.lastname: Shankle
authors.forename: J S
authors.initials: JS
authors.lastname: Farrow
authors.forename: M
authors.initials: M
authors.lastname: Dick
authors.forename: J M
authors.initials: JM
authors.lastname: Rozemuller
authors.forename: M A
authors.initials: MA
authors.lastname: Kuiper
authors.forename: E C
authors.initials: EC
authors.lastname: Wolters
authors.forename: J
authors.initials: J
authors.lastname: Zimmerman
authors.forename: C W
authors.initials: CW
authors.lastname: Cotman
mesh_terms: D000544:Alzheimer Disease / Q000134:cerebrospinal fluid*; D016564:Amyloid beta-Protein Precursor / Q000134:cerebrospinal fluid* / Q000737:chemistry / Q000276:immunology; D000911:Antibodies, Monoclonal; D015153:Blotting, Western; D006801:Humans; D012995:Solubility
chemical_list: D016564:Amyloid beta-Protein Precursor; D000911:Antibodies, Monoclonal