Introduction: Individuals in early stages of Alzheimer's disease are a targeted population for secondary prevention trials aimed at preserving normal cognition. Understanding within-person biomarker(s) change over time is critical for trial enrollment and design. Methods: Longitudinal cerebrospinal fluid samples from the Alzheimer's Disease Neuroimaging Initiative were assayed for novel markers of neuronal/synaptic injury (visinin-like protein 1, Ng, and SNAP-25) and neuroinflammation (YKL-40) and compared with β amyloid 42, tau, and phospho-tau181. General linear mixed models were used to compare within-person rates of change in three clinical groups (cognitively normal, mild cognitive impairment, and Alzheimer's disease) further defined by β amyloid status. Results: Levels of injury markers were highly positively correlated. Despite elevated baseline levels as a function of clinical status and amyloid-positivity, within-person decreases in these measures were observed in the early symptomatic, amyloid-positive Alzheimer's disease group. Discussion: Knowledge of within-person biomarker change will impact interpretation of biomarker outcomes in clinical trials that are dependent on disease stage.

Original languageEnglish
Pages (from-to)869-879
Number of pages11
JournalAlzheimer's and Dementia
Issue number7
StatePublished - Jul 2018


  • Cerebrospinal fluid
  • Longitudinal biomarkers
  • Neuronal injury


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