Familial Alzheimer disease: Decreases in CSF Aβ42 levels precede cognitive decline

CSF amyloid β-peptide 42 (Aβ42) levels in presymptomatic subjects with pathogenic mutations in the PS1 gene are significantly lower than in an age-matched control group. Consequently, in these subjects, there is a window of opportunity estimated as at least 4 to 12 years to evaluate the ability of any putative prophylactic therapy to decrease, arrest, or reverse abnormalities in Aβ42 metabolism many years before clinical symptoms of Alzheimer disease are otherwise likely to occur.