White Matter Abnormalities Track Disease Progression in PSEN1 Autosomal Dominant Alzheimer's Disease

J Alzheimers Dis. 2016;51(3):827-35. doi: 10.3233/JAD-150899.


PSEN1 mutations are the most frequent cause of autosomal dominant Alzheimer's disease (ADAD), and show nearly full penetrance. There is presently increasing interest in the study of biomarkers that track disease progression in order to test therapeutic interventions in ADAD. We used white mater (WM) volumetric characteristics and diffusion tensor imaging (DTI) metrics to investigate correlations with the normalized time to expected symptoms onset (relative age ratio) and group differences in a cohort of 36 subjects from PSEN1 ADAD families: 22 mutation carriers, 10 symptomatic (SMC) and 12 asymptomatic (AMC), and 14 non-carriers (NC). Subjects underwent a 3T MRI. WM morphometric data and DTI metrics were analyzed. We found that PSEN1 MC showed significant negative correlation between fractional anisotropy (FA) and the relative age ratio in the genus and body of corpus callosum and corona radiate (p < 0.05 Family-wise error correction (FWE) at cluster level) and positive correlation with mean diffusivity (MD), axial diffusivity (AxD), and radial diffusivity (RD) in the splenium of corpus callosum. SMC presented WM volume loss, reduced FA and increased MD, AxD, and RD in the anterior and posterior corona radiate, corpus callosum (p < 0.05 FWE) compared with NC. No significant differences were observed between AMC and NC in WM volume or DTI measures. These findings suggest that the integrity of the WM deteriorates linearly in PSEN1 ADAD from the early phases of the disease; thus DTI metrics might be useful to monitor the disease progression. However, the lack of significant alterations at the preclinical stages suggests that these indexes might not be good candidates for early markers of the disease.

Keywords: Alzheimer’s disease; diffusion tensor imaging; magnetic resonance imaging; presenilin 1; white matter.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aging / pathology
  • Alzheimer Disease / diagnostic imaging*
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / pathology
  • Brain / diagnostic imaging*
  • Brain / pathology
  • Cohort Studies
  • Diffusion Tensor Imaging
  • Disease Progression*
  • Family
  • Female
  • Heterozygote
  • Humans
  • Image Processing, Computer-Assisted
  • Magnetic Resonance Imaging
  • Male
  • Mental Status Schedule
  • Middle Aged
  • Mutation
  • Neuropsychological Tests
  • Organ Size
  • Presenilin-1 / genetics*
  • White Matter / diagnostic imaging*
  • White Matter / pathology


  • PSEN1 protein, human
  • Presenilin-1