| Abstrakt: |
Background: Two biomarkers for Alzheimer's disease (AD) are amyloid‐beta (Aβ) and tau aggregation. AD patients often experience comorbidities like metabolic dysfunction and/or sleep‐wake cycle disruption, but it is unclear whether this can be directly linked to Aβ or tau aggregation. Previous research shows mouse models overexpressing Aβ also experience metabolic and sleep dysfunction, independent of comorbidities like type‐2‐diabetes. Our lab previously demonstrated that central and peripheral metabolic changes are linked. This bidirectional relationship is well described in mouse models of Aβ overexpression; however, this relationship is relatively unexplored in mouse models of tauopathy. Therefore, our lab is investigating how central and peripheral metabolism relate to sleep‐wake disruption in the P301S PS19 mouse. Method: To investigate changes in peripheral metabolism, body weights are measured, and glucose tolerance tests are conducted on P301S PS19 and wild type female mice. Blood glucose levels are taken after fasting for four hours. Next, the mice are given an ip dose of 2g/kg glucose followed by blood glucose measurements in 15‐minute increments for two hours. Paired glucose and lactate biosensors placed within the mouse hippocampus track second by second metabolic fluctuations over three circadian days. Along with biosensors, EEG and EMG electrodes are positioned to record sleep‐wake cycles during this period. All methods completed on 3‐, 6‐, and 9‐month‐old P301S and wild type female mice. Result: While current experiments are ongoing, P301S mice become glucose sensitive where WT mice become glucose intolerant with age. Early analysis suggests pathology and age‐related differences in metabolism and sleep also develop over the circadian day. Our data suggests that tau aggregation increases peripheral glucose metabolism, in a manner different than Aβ pathology. Tau pathology disrupts normal sleep patterns where it decreases time spent in NREM and REM and alters EEG frequencies like delta, beta, and gamma. As age and pathology progress, cerebral metabolism of glucose and lactate is increased compared to age‐matched WT mice. Conclusion: We hypothesize tau pathology induced hyperexcitability alters sleep/wake cycles, peripheral and cerebral metabolism, and exacerbates pathology. Our current research is valuable in expanding knowledge of the relationship between metabolism, sleep, and tau in Alzheimer's disease. [ABSTRACT FROM AUTHOR] |
