Pre-symptomatic functional brain changes in PS1 E280A mutation carriers compared to other biomarkers: Pilot data from the Alzheimer's Prevention Initiative Biomarker project

mg of citalopram prior to the start of the central nervous system stable isotope labeling kinetics study of Abeta, as previously described. A lumbar catheter was placed and hourly sampling of blood and CSF was conducted during and after administration of a stable-isotope labeled amino acid (13C6-leucine). Metabolism of Abeta was measured using stable isotope labeling kinetics (SILK-Ab ) assay (as in Bateman et al., 2006) with the addition of stable isotope spike absolute quantitation (SISAQ ) to allow for quantitation of Abeta concentrations (C2N Diagnostics). Results: Placebo (n1⁄4 9) and citalopram (n1⁄4 11) treated subjects did not differ on any demographic variables. Citalopram-treated subjects had significantly lower mean total Abeta concentrations (36.7 +/10.5) ng/mL than placebo-treated (54.6 +/15.5) ng/mL (p 1⁄4 0.007) over the hours 5-36. During the same period there was a trend towards lower newly generated Abeta (p 1⁄4 0.06) in the citalopram group (7.5 +/1.3) ng/mL vs placebo (9.3 +/1.4) ng/mL however the groups did not differ in their fractional synthesis or clearance rates.Conclusions:We corroborate our prior findings in a prospective human study showing that citalopram lowers Abeta concentrations compared with placebo. We had also expected to see a lower rate of Abeta production and a decrease in newly generated Abeta, thus we are currently replicating and extending our results. The ability to decrease Abeta concentrations is potentially important as a preventive strategy for AD.