Cerebrospinal fluid biomarkers and cerebral atrophy in distinct clinical variants of probable Alzheimer's disease

Neurobiol Aging. 2015 Aug;36(8):2340-7. doi: 10.1016/j.neurobiolaging.2015.04.011. Epub 2015 Apr 25.


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.

Keywords: Alzheimer's disease; Amyloid; Atrophy; Cerebrospinal fluid; Magnetic resonance imaging; Tau.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / diagnosis*
  • Alzheimer Disease / pathology*
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Atrophy
  • Biomarkers / cerebrospinal fluid
  • Brain / pathology*
  • Female
  • Gray Matter / pathology
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Peptide Fragments / cerebrospinal fluid*
  • Severity of Illness Index
  • tau Proteins / cerebrospinal fluid


  • Amyloid beta-Peptides
  • Biomarkers
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • tau Proteins