title: Association between cerebrospinal fluid tau and brain atrophy is not related to clinical severity in the Alzheimer's disease continuum.
abstract: We aimed to assess the association between core cerebrospinal fluid (CSF) biomarkers, regional brain atrophy and clinical severity in the Alzheimer's disease (AD) continuum, as well as to investigate how cognitive reserve (CR) may modulate these putative associations. Forty-nine subjects (11 controls, 10 patients with subjective memory complaints, 19 with mild cognitive impairment and 9 mild AD) underwent lumbar puncture and high-resolution magnetic resonance imaging (MRI). CSF amyloid-β(1-42) (Aβ(1-42)), total tau (t-tau) and phosphorylated tau (p-tau(181)) were determined. Voxel-based morphometry (VBM) was applied and multiple regression analyses for the whole sample were carried out. Clinical severity was adjusted using the Clinical Dementia Rating Sum of Boxes score (CDR-SB). A negative correlation between t-tau levels and grey matter (GM) volume in temporo-parietal regions was found, regardless of CDR-SB score. In contrast, the negative correlation between p-tau(181) and GM volume was largely explained by clinical severity, except in the posterior cingulate cortex. CR did not significantly modify these correlations. Aβ(1-42) levels were not related to GM volume but were related to clinical severity, an association that was attenuated when CR was considered. In conclusion, the present findings reflect that t-tau CSF concentrations are associated with GM atrophy in neuropathologically relevant areas across the AD continuum, whereas the p-tau(181) association is largely dependent on the degree of clinical severity. The relationship between CSF Aβ(1-42) and clinical severity seems to be modulated by CR, suggesting that there may be subjects with pathological levels of Aβ(1-42) and high CR estimates who remain clinically asymptomatic.
authors.affiliation: Alzheimer's disease and other Cognitive Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Catalonia, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Solé-Padullés
authors.forename: Albert
authors.initials: A
authors.lastname: Lladó
authors.forename: David
authors.initials: D
authors.lastname: Bartrés-Faz
authors.forename: Juan
authors.initials: J
authors.lastname: Fortea
authors.forename: Raquel
authors.initials: R
authors.lastname: Sánchez-Valle
authors.forename: Beatriz
authors.initials: B
authors.lastname: Bosch
authors.forename: Anna
authors.initials: A
authors.lastname: Antonell
authors.forename: José Luis
authors.initials: JL
authors.lastname: Molinuevo
authors.forename: Lorena
authors.initials: L
authors.lastname: Rami
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D001284:Atrophy / Q000209:etiology / Q000473:pathology; D001921:Brain / Q000473:pathology*; D001931:Brain Mapping; D003072:Cognition Disorders / Q000209:etiology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000134:cerebrospinal fluid* / Q000150:complications* / Q000473:pathology; D013223:Statistics as Topic; D011795:Surveys and Questionnaires; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; C054369:MAPT protein, human; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins