[The DIAN study]

Brain Nerve. 2013 Oct;65(10):1179-84.
[Article in Japanese]

Abstract

The DIAN study compared the pathophysiological markers between carriers and non-carriers of mutation for autosomal dominant Alzheimer's disease (AD). They used the participant's age at baseline assessment and the parent's age at the onset of symptoms of AD to calculate the estimated delay in symptom onset. The study revealed that the biomarker change, which is the reduction of Aβ42 in the CSF of the carrier's brain, started approximately 15-20 years prior to the onset of symptoms. Subsequently, a chronological series of events took place: deposition of fibrillar Aβ as measured by positron emission tomography with the use of Pittsburgh compound B, increase in tau protein in the CSF, hippocampal atrophy and hypometabolism of FDG-PET, and cognitive and clinical changes. The researchers planned to start the prevention trial with 2 monoclonal antibodies and a BACE inhibitor. In contrast, the API study is the clinical trial of the anti-amyloid monoclonal antibody therapy associated with the early-onset familial AD (EOAD), which carries the PSEN1 E280A mutation. This study also showed changes in the same biomarker as reported in the DIAN study. Anti-amyloid treatment in asymptomatic AD (A4) is a prevention trial aimed at treating older individuals with normal cognition but at risk of developing AD dementia on the basis of having biomarker evidence of amyloid (preclinical AD). They selected solanezumab for the anti-amyloid treatment for A4.

Publication types

  • English Abstract
  • Review

MeSH terms

  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / metabolism
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Biomarkers / metabolism
  • Humans
  • Mutation / genetics*
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism
  • Sex Characteristics

Substances

  • Amyloid beta-Peptides
  • Biomarkers
  • Peptide Fragments