Altered levels of plasma kallikrein‐7 in prodromal Alzheimer’s disease

Background The accumulation of Aβ is thought to be dependent on imbalances in production or clearance of the peptide. At the core of the production and the breakdown of Aβ are changes in the activity of proteases. Several studies have suggested that the level and activity of brain proteases involved in the clearance pathway are perturbed in the disease. Given that AD is essentially a protease disease, we sought to determine if key proteases were altered in the blood plasma fraction, reflecting changes that are occur in the brain. Method We used a fast commercial tool to investigate the level of 34 proteases in plasma between healthy controls and AD patients. Next we used an ELISA and western blot assays to validate results from the discovery assay. Result We discovered that the protease kallikrein‐7 (KLK7) was significantly elevated in AD plasma. We then asked how early in the disease time course is KLK7 elevated. We used plasma from cognitively normal cases (n=120) with either high or low levels of brain amyloid based on PET imaging and found that KLK7 leaves are decreased. Conclusion These results suggest that the plasma level of Kallikrein‐7 may be an important tool in detecting elevated levels of brain amyloid before symptoms of AD become apparent.