Saliva biomarkers for Alzheimer’s disease risk in a rat model of low and high intrinsic exercise capacity

Abstract

AbstractBackgroundIdentifying a natural‐occurring animal model for Alzheimer's Disease (AD) and a non‐invasive early AD diagnostic are significant AD research challenges. Previously, we developed rat models by selectively breeding for low and high intrinsic exercise capacity. We found that compared to High Capacity Runners (HCR), Low Capacity Runners (LCR) have a reduced lifespan and greater risk for cardiovascular disease, diabetes, and obesity.1 LCR exhibit neurodegeneration, impaired memory, and decreased hippocampal neurogenesis. Saliva is a relatively new AD‐associated research area, and as a bioanalytic,2 is an important extension of protein changes in the autonomic nervous system and immune response. Our goal is to determine whether salivary biomarkers link with exercise capacity and brain health in LCR and HCR rats.MethodWe studied three‐generations of female rats (6 months: 9 LCR, 10 HCR), (20 months: 8 LCR, and 8 HCR), and (26 months: 7 LCR, 6 HCR). We assessed exercise capacity using a treadmill running test and cognitive function using a Y‐maze. Salivary gland weight and salivary flow rate (SFR) of a submandibular gland (SMG) were measured and compared. The acinar cells proliferation of SMG was assessed by IHC using PCNA. Biomarkers for p‐tau ser610 and amyloid‐beta were investigated in hippocampus tissue, saliva, and plasma using ELISA.ResultThe LCR and HCR groups were significantly different for maximal treadmill running distance and time spent in novel arm of the Y‐Maze. The SFR and acinar cell proliferation were higher in HCR. The size and mass of SMG were bigger in LCR rats. Levels of p‐tau in saliva and plasma were markedly greater in LCR than HCR, but no differences in the hippocampus. There was no difference between the two groups in the hippocampus or saliva regarding amyloid‐beta levels. However, it was significantly increased in plasma in the LCR group compared with the HCR group.ConclusionTaken together, the findings of this study provide experimental evidence that saliva biomarkers are significantly increased in the LCR group compared with the HCR group. This is the first study using novel and unexplored preclinical rat models that combines exercise capacity with AD risk by utilizing saliva biomarkers.