The etiology of Alzheimer's disease (AD) is multifaceted with both genetic and modifiable environmental exposure (exposome) factors contributing to cognitive decline. Metabolic syndrome, including insulin resistance, increases the risk for developing AD, which we have observed in AβPP/PS1 mice. We hypothesized that altering environmental temperature (eT) exposure would improve the metabolic profile of AD mice thereby alleviating cognitive deficits. Starting at 6 months of age (mild amyloid pathology and cognitive impairment), male and female AβPP/PS1, APPNL-F/NL-F , and genetic background control C57BL/6 mice were chronically housed at either 16, 23, or 30°C for 6 months. At 12 months of age, mice were assayed for insulin sensitivity, glucose tolerance, and cognitive performance using the Morris water maze (MWM) behavioral paradigm. Plasma, hippocampal, and peripheral (adipose, hepatic, and pancreatic) samples were procured postmortem and tissue-specific markers of amyloid accumulation and metabolism were assayed. In male mice, chronic exposure to 16°C eT reduced body weight, but had no effect on metabolism nor cognition (Figure 1). Male AD mice exposed to 30°C eT had reduced body weight, improved glucose tolerance, and better performance on the MWM. Plasma concentrations of insulin-like growth factor 1 (IGF-1) and leptin were also decreased in male AD mice at 30°C eT. In female mice, chronic exposure to either eT did not alter body weight, nor cognition. However, 30°C eT improved insulin sensitivity of female C57BL/6 and AβPP/PS1 mice with an corresponding increase in IGF-1 plasma levels. Despite the known improvements on metabolic factors by increasing thermogenesis, chronic exposure to 16°C did not improve the metabolic profile of control or AD mice. Unexpectedly, 30°C eT improved the metabolic profile of male and female C57BL/6 and AβPP/PS1 mice, but cognitive performance was only improved in male mice. Work is ongoing to elucidate markers of glucose metabolism and amyloid pathology in post mortem tissue to better interpret these sexually dimorphic results. This work was supported by the National Institutes of Health (R01 AG057767, R01 AG061937), the Illinois Department of Public Health (03282005H), CARE, and the Kenneth Stark Endowment.