title: Could clinical profile influence CSF biomarkers in early-onset Alzheimer disease?
abstract: In common forms of Alzheimer disease (AD), anterograde memory impairment is the first deficit to occur. However, the disease, especially in its presenile forms, may also manifest itself through initial deficits that are predominantly of a nonmemory type. These distinct clinical profiles, which reflect the distinct topography of the underlying pathologic processes, may also differ in terms of their cerebrospinal fluid (CSF) markers. The aim of this study was to assess the levels of total tau, phosphorylated tau, and amyloid-beta 42 peptide in the CSF of "atypical" (nonmemory) early-onset AD patients. CSF biomarkers were evaluated in 22 atypical patients, and compared with those from a group of 13 "typical" patients, with a memory onset form of the disease. Our results show that independently of age, disease duration, education level, and clinical severity indices, patients with an atypical onset have significantly higher levels of total tau in the CSF (P=0.023). These findings indicate that an assessment of CSF biomarkers may be of particular use in the clinical diagnosis of "atypical-onset" forms of early-onset AD in which the initial symptoms involve language and visuospatial abilities rather than memory. In addition, they highlight the heterogeneity of pathologic processes in AD, suggesting more intense degeneration in the forms of the disease that primarily involve neocortical structures.
authors.affiliation: Service de Neurologie et Neuropsychologie, AP-HM, Hôpital de la Timone, Université de la Méditerranée, Marseille, France.
authors.forename: Lejla
authors.initials: L
authors.lastname: Koric
authors.forename: Olivier
authors.initials: O
authors.lastname: Felician
authors.forename: Eric
authors.initials: E
authors.lastname: Guedj
authors.forename: Anne Michele
authors.initials: AM
authors.lastname: Hubert
authors.forename: Julien
authors.initials: J
authors.lastname: Mancini
authors.forename: Jose
authors.initials: J
authors.lastname: Boucraut
authors.forename: Mathieu
authors.initials: M
authors.lastname: Ceccaldi
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D001921:Brain / Q000473:pathology; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007118:Immunoassay; D016015:Logistic Models; D008297:Male; D008569:Memory Disorders / Q000134:cerebrospinal fluid; D008875:Middle Aged; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D010766:Phosphorylation; D014055:Tomography, Emission-Computed; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; C054369:MAPT protein, human; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins