The two major pathologies that are linked to Alzheimer's disease (AD), include extracellular beta-amyloid (Abeta) plaques and intracellular neurofibrillary tangles (NFTs) comprised of hyper-phosphorylated Tau (p-Tau) [1]. Evidence suggests that Abeta and p-Tau accumulation are due to lack of autophagic clearance in AD [2-9], thus autophagy is one mechanism to degrade beta-amyloid and p-Tau [10-13]. Importantly, activation of the tyrosine kinase Abelson (Abl) is associated with increased p-Tau levels in several AD models [13-21] and human post-mortem AD brains [13, 21, 22]. Nilotinib (AMN107) is a second generation Bcr-Abl inhibitor, which is clinically effective in adult chronic myeloid leukemia (CML) [23]. Our pre-clinical data demonstrate that Nilotinib (Tasigna) penetrates the brain and promotes autophagic degradation of beta-amyloid and p-Tau, attenuates inflammation and improves cognition [13, 20, 21, 24]. The simultaneous autophagic degradation of p-Tau and beta-amyloid [13, 21] and reduction of neuro-inflammation, which is a characteristic of AD [25], suggest that Nilotinib may be an effective AD therapy via Abl inhibition. Thus, overall we hypothesize that low daily doses of Nilotinib will alter CSF Abeta40/42, total and p-Tau181 levels, modulate blood and CSF immunity and improve cognitive function in mild to moderate AD patients.