CEREBROSPINAL-FLUID LEVELS OF AMYLOID PRECURSOR PROTEIN AND AMYLOID BETA-PEPTIDE IN ALZHEIMERS-DISEASE AND MAJOR DEPRESSION - INVERSE CORRELATION WITH DEMENTIA SEVERITY

Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized by progressive dementia that ultimately leads to death, Histopathological hallmarks of AD include brain amyloid deposits and neurofibrillary tangles, Major depression is a frequent diagnosis in e very gerontopsychiatric clinic that sees patients with both cognitive and affective disorders, Many depressed patients, in fact, are clinica lly characterized by cognitive impairments. Thus, an assay that exclud es -or confirms -probable AD in cognitively impaired patients is desir able, Such assays may use protein markers that are derived from such h istopathologically relevant molecules as the amyloid precursor protein (APP) and its derivatives including the amyloid beta-peprides (A beta ), To evaluate the differential diagnostic properties of cerebrospinal fluid (CSF) AB and secreted soluble ectodomain (APPs), we quantitated CSF levels of these measures in AD patients and compared them to age- matched control patients with major depression, CSF levels of APPs and A beta were similar in patients with AD or major depression, and the apolipoprotein E genotype had no Influence on CSF levels of A beta in AD patients. Measurement of A beta peptide using a novel zinc/copper c apture ELISA that detects aggregated A beta peptides as well demonstra ted similar levels in AD and major depression, In AD patients, CSF lev els of total A beta (A beta 1-40 plus A beta 1-42) were inversely corr elated with a functional measure of dementia severity (NOSGER), sugges ting that CSF levels of A beta decrease with advancing severity of AD, Thus, CSF levels of A beta are not useful for the differentiation of AD from major depression, However, CSF levels of A beta reflect the se verity of dementia and may be useful as biological markers of the stag e of the disease.