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

and Dominantly Inherited Alzheimer Network (DIAN), Chengjie Xiong, Lena M. McCue, Virginia Buckles, Elizabeth Grant, Folasade Agboola, Dean Coble, Randall J. Bateman, Anne M. Fagan, Tammie L.S. Benzinger, Jason Hassenstab, Suzanne E. Schindler, Eric McDade, Krista Moulder, Brian A. Gordon, Carlos Cruchaga, Gregory S. Day, Takeshi Ikeuchi, Kazushi Suzuki, Ricardo F. AllegriJonathan Vöglein, Johannes Levin, John C. Morris

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)2923-2932
Number of pages10
JournalAlzheimer's and Dementia
Volume19
Issue number7
DOIs
StatePublished - Jul 2023

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)

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