Introduction: The contribution of genetic and environmental factors to the relation between cerebrospinal fluid (CSF) biomarkers and cognitive decline in preclinical Alzheimer's disease remains unclear. We studied this in initially cognitively normal monozygotic twins.

Methods: We included 122 cognitively normal monozygotic twins (51 pairs) with a follow-up of 4.3 ± 0.4 years. We first tested associations of baseline CSF Aβ1-42/1-40 ratio, total tau (t-tau), and 181-phosphorylated-tau (p-tau) status with subsequent cognitive decline using linear mixed models, and then performed twin specific analyses.

Results: Baseline abnormal amyloid-β and tau CSF markers predicted steeper decline on memory (p ≤ .003) and language (p ≤ 0.04). Amyloid-β and p-tau markers in one twin predicted decline in memory in the co-twin and tau markers in one twin predicted decline in language in the co-twin (r range -0.26,0.39; p's ≤ .02).

Discussion: These results suggest that memory and language decline are early features of AD that are in part determined by the same genetic factors that influence amyloid-β and tau regulation.

Original languageEnglish
Article numbere12346
Pages (from-to)e12346
Number of pages12
JournalAlzheimer's and Dementia: Translational Research and Clinical Interventions
Issue number1
Early online date20 Sept 2022
Publication statusPublished - 25 Sept 2022


  • amyloid-beta
  • biomarkers
  • cerebrospinal fluid
  • cognition
  • cognitive decline
  • longitudinal design
  • monozygotic twins
  • neuropsychology
  • preclinical Alzheimer's disease
  • tau

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