Werner Naser

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 β-peptides (Aβ). To evaluate the differential diagnostic properties of cerebrospinal fluid (CSF) Aβ 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 Aβ were similar in patients with AD or major depression, and the apolipoprotein E genotype had no influence on CSF levels of Aβ in AD patients. Measurement of Aβ peptide using a novel zinc/copper capture ELISA that detects aggregated Aβ peptides as well demonstrated similar levels in AD and major depression. In AD patients, CSF levels of total Aβ (Aβ1–40 plus Aβ1–42) were inversely correlated with a functional measure of dementia severity (NOSGER), suggesting that CSF levels of Aβ decrease with advancing severity of AD. Thus, CSF levels of Aβ are not useful for the differentiation of AD from major depression. However, CSF levels of Aβ reflect the severity of dementia and may be useful as biological markers of the stage of the disease.