Longitudinal cerebrospinal fluid biomarker measurements in preclinical sporadic Alzheimer's disease: A prospective 9-year study

INTRODUCTION: Ascertainment of the pattern and temporal change of biomarkers in preclinical (asymptomatic) sporadic Alzheimer's disease (AD) will increase knowledge about early pathogenesis and facilitate interventional therapeutic trials. METHODS: In this prospective longitudinal study, repeated cerebrospinal fluid (CSF) collections and cognitive evaluations were performed in cognitively healthy elderly individuals during a 9-year period. RESULTS: Low CSF β-amyloid (Aβ)(42) levels predicted subsequent development of clinical AD 9 years later. Noteworthy, one-third of individuals with pathologically low baseline Aβ(42) levels remained cognitively intact during follow-up. No further decrease in Aβ(42) was seen in those with low levels already at baseline. DISCUSSION: CSF Aβ(42) predicts sporadic AD at least 9 years before dementia onset and has plateaued already at this time. However, many individuals can harbor brain amyloid accumulation over a decade without signs of cognitive deterioration, which could implicate how CSF biomarkers are used to identify preclinical AD in future interventional therapeutic trials.