Results Concentrations of amyloid-beta (Aβ) 42 in the CSF appeared to decline 25 years before expected symptom onset. We conducted cross-sectional analyses of baseline data in relation to estimated years from expected symptom onset in order to determine the relative order and magnitude of pathophysiological changes. We used the participant's age at baseline assessment and the parent's age at the onset of symptoms of Alzheimer's disease to calculate the estimated years from expected symptom onset (age of the participant minus parent's age at symptom onset). Methods In this prospective, longitudinal study, we analyzed data from 128 participants who underwent baseline clinical and cognitive assessments, brain imaging, and cerebrospinal fluid (CSF) and blood tests. Morris, M.D., for the Dominantly Inherited Alzheimer Network N Engl J Med 2012 367:795-804 DOI: 10.1056/NEJMoa1202753 open through September 5, 2012. Sperling, M.D., Stephen Salloway, M.D., and John C.
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