Biomarker profiles of Alzheimer's disease and dynamic of the association between cerebrospinal fluid levels of β-amyloid peptide and tau

• Published in: PloS one 2019-05, Vol.14 (5), p.e0217026-e0217026
• Main Authors: Lafirdeen, Aysha S Mohamed, Cognat, Emmanuel, Sabia, Severine, Hourregue, Claire, Lilamand, Matthieu, Dugravot, Aline, Bouaziz-Amar, Elodie, Laplanche, Jean-Louis, Hugon, Jacques, Singh-Manoux, Archana, Paquet, Claire, Dumurgier, Julien
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Aging; Alzheimer Disease - cerebrospinal fluid; Alzheimer's disease; Amyloid beta-Peptides - cerebrospinal fluid; Amyloidosis; Amyloidosis - cerebrospinal fluid; Apolipoprotein E4; Apolipoproteins E - genetics; Biochemistry; Biochemistry, Molecular Biology; Biology and Life Sciences; Biomarkers; Cerebrospinal fluid; Cognition Disorders - cerebrospinal fluid; Cognitive ability; Cognitive Dysfunction - cerebrospinal fluid; Dementia; Disease Progression; Epidemiology; Female; France; Geriatry and gerontology; Hospitals; Human health and pathology; Humans; Hypotheses; Life Sciences; Longitudinal Studies; Male; Medicine and Health Sciences; Memory; Memory Disorders - cerebrospinal fluid; Middle Aged; Neurobiology; Neurodegeneration; Neurodegenerative Diseases - cerebrospinal fluid; Neurology; Neurons and Cognition; Neurosciences; Peptide Fragments - cerebrospinal fluid; Peptides; Physical Sciences; Regression Analysis; Regression models; Research and Analysis Methods; Spinal Puncture; Studies; Tau protein; tau Proteins - cerebrospinal fluid; β-Amyloid
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0217026

To investigate the relationship between cerebrospinal fluid (CSF) β-amyloid peptide (Aβ42) and CSF Tau in a large population of patients referred to memory clinics for investigation of cognitive dysfunction. We analyzed Alzheimer's disease (AD) biomarkers in CSF taken from 3565 patients referred to 18 French memory clinics. Patients were classified into four profiles according to levels of CSF biomarkers (A: amyloidosis, N: neurodegeneration). The association between CSF Tau and CSF Aβ42 were analyzed using general linear regression models, in the overall population and stratified by biomarkers profiles. We compared linear and quadratic models using Akaike information criterion. We also assessed change in biomarker profiles in a subset of patients who had 2 assessments of biomarkers. CSF Tau was negatively associated with CSF Aβ42 in the overall population, following a non-linear quadratic model. However, the nature of this association was different in the 4 profiles: positive association in A-N- profile, negative association in A-N+ and A+N+ profiles, lack of association in A+N- patients. When considering patients with longitudinal data on profiles, 36% of those initially classified as A-N+ evolved to an A+N+ profile. The nature of the association between CSF Aβ42 and CFS Tau depends on the A/N profiles of patients. These results suggest an increase in CSF Aβ42 early in the disease before its decline while tau pathology progresses, this pattern is particularly observed in non-APOE4 subjects. This phenomenon may explain why some patients with neurodegeneration only markers convert to an AD profile (A+N+) over time.