Cerebrospinal fluid levels of amyloid precursor protein and amyloid β-peptide in Alzheimer's 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 every gerontopsychiatric clinic that sees patients with both cognitive and affective disorders, Many depressed patients, in fact, are clinically characterized by cognitive impairments. Thus, an assay that excludes -or confirms -probable AD in cognitively impaired patients is desirable, Such assays may use protein markers that are derived from such histopathologically 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 capture ELISA that detects aggregated A beta peptides as well demonstrated similar levels in AD and major depression, In AD patients, CSF levels of total A beta (A beta 1-40 plus A beta 1-42) were inversely correlated with a functional measure of dementia severity (NOSGER), suggesting 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 severity of dementia and may be useful as biological markers of the stage of the disease.