Aims

Increasing evidence support that metabolic dysregulation plays a key role in Alzheimer’s disease (AD) etiology. Previous research demonstrated male AβPP/PS1 mice have an impaired metabolic profile compared to age-matched C57BL/6J littermate controls. We hypothesized that chronically altering the environmental temperature (eT) could improve their metabolic profile thereby ameliorating cognitive deficits.

Methods

Starting at 6 months of age (mild amyloid pathology and cognitive impairment) male AβPP/PS1 mice were housed at either 23°C (standard), or 30°C (thermoneutral) eT for 6 months. Following 6 months of chronic eT treatment (12 months of age), mice were assayed for insulin sensitivity, glucose tolerance, and cognitive performance using the Morris water maze (MWM) behavioral paradigm. Post mortem analysis of circulating plasma levels elucidated changes in markers associated with successful aging.

Results

AβPP/PS1 mice housed in thermoneutral eT had reduced body weight compared to standard eT. Male AβPP/PS1 in thermoneutral eT had improved glucose tolerance as well as cognitive performance in the MWM. Plasma levels of insulin-like growth factor 1, leptin, and receptor for advanced glycation endproducts were reduced in AβPP/PS1 mice housed at thermoneutral eT.

Conclusions

A thermoneutral eT may provide a nonpharmacological strategy to improve metabolism and cognitive performance during the early stages of AD. Ongoing studies will elucidate changes in peripheral and cerebral markers of inflammation as well as soluble / insoluble amyloid accumulation.

This work was supported by: NIH R01AG057767 and R01AG061937.