Grant: Project Grant

The accumulation of abnormal tau proteins in the brain is the prevalent cause of dementia in Alzheimer's disease (AD). Nearly 750,000 Canadians are living with AD. Unless new, effective, therapies are found this number could exceed 1.4 million by 2031. This grant proposal focusses on the investigation of potential therapeutic benefits of Lithium at very low doses to halt or delay the harmful brain tau pathology. At these doses no adverse effects are expected, thus permitting the needed long-term treatment. These objectives are supported by our prior published evidence showing that prolonged treatments with extremely low doses of Lithium notably arrested amyloid pathology, brain inflammation and improved cognition in rats with AD-like amyloid pathology. Our objectives are also supported by the evidence that our Lithium microdose preparation effectively reaches the brain. If successful, the project should have clinical application in a short-term. For these studies, we will apply genetically modified rats which accumulate pathological forms of tau protein in their brain. This genetic alteration results in neuronal loss, brain atrophy and cognitive impairments, similarly as in patients with Alzheimer's. These genetically modified rats modelling human tau pathology will be treated with microdoses of Lithium to examine their effects on brain health and cognition. We will test micro-Lithium doses at two stages of the "human-like" tau pathology in transgenic rats: at an early stage when cognitive symptoms are not yet present and at a late stage when the tau pathology is well-established provoking a marked cognitive decline, equivalent to dementia stages in the human. Our research team is well placed to carry out this study. The Lab has access to all the necessary techniques and equipment to perform the needed behavioral, brain anatomical, cellular, and biochemical analysis to assess drug-induced therapeutic effects on the AD-like tau pathology and cognitive outcomes.