Cross-sectional and longitudinal comparisons of biomarkers and cognition among asymptomatic middle-aged individuals with a parental history of either autosomal dominant or late-onset Alzheimer's disease

Alzheimers Dement. 2023 Jul;19(7):2923-2932. doi: 10.1002/alz.12912. Epub 2023 Jan 14.


Background: Comparisons of late-onset Alzheimer's disease (LOAD) and autosomal dominant AD (ADAD) are confounded by age.

Methods: We compared biomarkers from cerebrospinal fluid (CSF), magnetic resonance imaging, and amyloid imaging with Pittsburgh Compound-B (PiB) across four groups of 387 cognitively normal participants, 42 to 65 years of age, in the Dominantly Inherited Alzheimer Network (DIAN) and the Adult Children Study (ACS) of LOAD: DIAN mutation carriers (MCs) and non-carriers (NON-MCs), and ACS participants with a positive (FH+) and negative (FH-) family history of LOAD.

Results: At baseline, MCs had the lowest age-adjusted level of CSF Aβ42 and the highest levels of total and phosphorylated tau-181, and PiB uptake. Longitudinally, MC had similar increase in PiB uptake to FH+, but drastically faster decline in hippocampal volume than others, and was the only group showing cognitive decline.

Discussion: Preclinical ADAD and LOAD share many biomarker signatures, but cross-sectional and longitudinal differences may exist.

Keywords: Alzheimer's disease (AD); Pittsburgh compound-B (PiB); autosomal dominant Alzheimer's disease (ADAD), cerebrospinal fluid (CSF); magnetic resonance imaging (MRI); positron emission tomography (PET).

Publication types

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

MeSH terms

  • Adult
  • Alzheimer Disease* / cerebrospinal fluid
  • Alzheimer Disease* / diagnostic imaging
  • Alzheimer Disease* / genetics
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Biomarkers / cerebrospinal fluid
  • Cognition
  • Cross-Sectional Studies
  • Humans
  • Middle Aged
  • Parents
  • Positron-Emission Tomography


  • Amyloid beta-Peptides
  • Biomarkers