Grant: Travel Awards - Institute Community Support

Alzheimer disease (AD) incidence is expected to more than double by the year 2050. Considering that less than 10% of AD cases are the result of genetic factors, external elements must be involved. Animal studies relying on humanized genetic mutations have been useful for studying the pathology of AD, but non-genetic models are now needed to elucidate the factors that contribute to the etiology of the far more prevalent late-onset form of the disease. These potential factors - obesity, chronic stress, and inflammation - are quickly becoming the norm in our society rather than the exception. Disturbingly, each of these conditions have been shown to contribute to mild neurodegeneration in isolation. Could these rising conditions be responsible for the growing AD epidemic? Further, high sodium diets and diuretics (coffee) increase the excretion of neuroprotective minerals from the kidney. One such mineral - lithium - may possess the ability to counteract the deleterious effects of high-sucrose and inflammation in the brain; could lithium deficiency thus be contributing to the rising incidence of AD? By combining low-dose intraperitoneal injections (0.1 mg/kg delivered once/month for 3 months) of the endotoxin lipopolysaccharide (LPS) with the addition of 20% sucrose (hS) to the animal drinking water (for 6 months), we explore the individual and cumulative effects of chronic inflammation and excess caloric intake on wild-type female mice. Also, the prophylactic potential of lithium against neurodegeneration was assessed via the addition of trace lithium orotate to the drinking water of hS-LPS (hSL) treated animals. Behavioral testing demonstrated an hS-induced disruption of learning and memory, and an hSL-induced increase in anxiety-like behavior; lithium blocked these effects. Biochemical assessments revealed that hS, and to a lesser extent hSL, precipitated a neurodegenerative phenotype consistent with early AD-like pathology that was antagonized by lithium treatment.