title: Cerebrospinal fluid biomarkers and cerebral atrophy in distinct clinical variants of probable Alzheimer's disease.
abstract: Different clinical variants of probable Alzheimer's disease (AD) share underlying plaques and tangles but show distinct atrophy patterns. We included 52 posterior cortical atrophy, 29 logopenic variant primary progressive aphasia, 53 early-onset and 42 late-onset AD patients, selected for abnormal cerebrospinal fluid (CSF)-amyloid-beta42, with CSF and magnetic resonance imaging data available. Bootstrapping revealed no differences in the prevalence of abnormal CSF total-tau and phosphorylated-tau between probable AD variants (range total-tau: 84.9%-92.3%, phosphorylated-tau: 79.2%-93.1%, p > 0.05). Voxelwise linear regressions showed various relationships between lower CSF-Aβ42 and syndrome-specific atrophy, involving precuneus, posterior cingulate, and medial temporal lobe in early-onset AD, occipital cortex and middle temporal gyrus in posterior cortical atrophy; anterior cingulate, insular cortex and precentral gyrus (left > right) in logopenic variant primary progressive aphasia; and medial temporal lobe, thalamus, and temporal pole in late-onset AD (all at p < 0.001 uncorrected). In contrast, CSF-tau was not related to gray matter atrophy in any group. Our findings suggest that lower CSF-amyloid-beta42 - and not increased total-tau and phosphorylated-tau - relates to reduced gray matter volumes, mostly in regions that are typically atrophied in distinct clinical variants of probable AD.
authors.affiliation: Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, CA, USA; Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, CA, USA; Department of Neurology & Alzheimer Center, VU University Medical Center, Amsterdam, The Netherlands; Department of Radiology & Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: r.ossenkoppele@vumc.nl.
authors.forename: Rik
authors.initials: R
authors.lastname: Ossenkoppele
authors.affiliation: Department of Veterans Affairs Medical Center, Center for Imaging of Neurodegenerative diseases, San Francisco, CA, USA; Institute of Neuroscience and Physiology, Laboratory of Clinical Neurochemistry, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Niklas
authors.initials: N
authors.lastname: Mattsson
authors.affiliation: Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Charlotte E
authors.initials: CE
authors.lastname: Teunissen
authors.affiliation: Department of Radiology & Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.affiliation: Department of Neurology & Alzheimer Center, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Yolande
authors.initials: Y
authors.lastname: Pijnenburg
authors.affiliation: Department of Neurology & Alzheimer Center, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Philip
authors.initials: P
authors.lastname: Scheltens
authors.affiliation: Department of Neurology & Alzheimer Center, VU University Medical Center, Amsterdam, The Netherlands; Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Wiesje M
authors.initials: WM
authors.lastname: van der Flier
authors.affiliation: Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, CA, USA; Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, CA, USA.
authors.forename: Gil D
authors.initials: GD
authors.lastname: Rabinovici
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D001284:Atrophy; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000473:pathology*; D005260:Female; D066128:Gray Matter / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D012720:Severity of Illness Index; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins
keywords: Alzheimer's disease; Amyloid; Atrophy; Cerebrospinal fluid; Magnetic resonance imaging; Tau