Aβ-specific antibodies induced by active immunotherapy CAD106 engage Aβ in plasma in AD patients

contact with the interstitial fluid of the brain, allowing for the analysis of biochemical changes that may be related to the disease. The levels of soluble amyloid precursor protein (sAPP) alpha and beta in the CSF have both been investigated as potential biomarkers for AD. Some studies have suggested the levels of sAPPb are lower in subjects with AD, other reports have shown that both sAPPa and sAPPb are increased in AD subjects. Potentially the lack of consistency in these results could be due to fluctuations in the levels of sAPP in the CSF. Intrasubject CSF levels of Ab have been shown to significantly increase when sampling occurred frequently over 24 hours. To address this, we have examined CSF samples taken multiple times over a 24 hour period from subjects with AD or from age-matched controls.Methods: CSF samples were collected by lumbar drain with an indwelling catheter at 0h,1h,4h,8h,12h,18h and 24h during a 24-hour period from 15mild-to-moderate AD patients and 7 non-demented age matched control subjects (CT). sAPPa and sAPPb were measured usingMSD duplex electro chemiluminescence assays.Results:Both sAPPa and sAPPb were detectable in CSF from mild-to-moderate AD and CT subjects. sAPPa and sAPPb levels in AD CSF did not show significant diurnal fluctuations across the time points during a 24-hour period, however, far more variability was observed in CSF from age-matched controls. The CV across the time points was approximately 10% for AD subjects, and 40% for age-matched controls. On average, the levels of both sAPPa and sAPPb were lower in AD subjects relative to age-matched controls at all time points measured. Conclusions:Our results show levels of sAPPa and sAPPbwere consistent across multiple time points in subjects with AD, however they were variable in CSF of age-matched controls. The source of the variability in sAPP CSF levels in control subjects is not known, however, the results suggest caution should be used for employing these analytes as diagnostic biomarkers for determining the presence of Alzheimer’s disease.