Brainstem pathology induces peripheral changes correlating with hippocampal markers of Alzheimer's disease in animal model

Abstract

Alzheimer's disease (AD) and related tauopathies are difficult to diagnose in early phase and their diseases modifying treatment is still missing. Epidemiological studies indicate relationships between AD and level of leptin in blood. However, the mechanistic link behind this association is not yet defined. Here, we investigated the link between selected metabolic parameters including leptin and pathogenic markers of neurodegeneration in a transgenic rat model of AD.Brains of transgenic rats expressing human truncated tau protein, whose primary sequence was designed according to AD‐core tau protein, were analysed in pre‐symptomatic and terminal phase of disease. The data were correlated with biochemical parameters such as glucose, insulin and lipids in plasma. We found that development of AD pathology leads to reduction of body weight accompanied with significant decrease in level of plasma leptin in transgenic animal model of sporadic AD. The plasma leptin inversely and significantly correlates with amount of hippocampal tau proteins hyperphosphorylated on several AD‐specific epitopes. Moreover, the strong inverse correlation between the load of neurofibrillary pathology and peripheral levels of leptin was observed.We provide a molecular evidence and experimental confirmation for association of circulating leptin and early stage of neurofibrillary degeneration in hippocampus, thus leptin could serve as a convenient peripheral biomarker, which can help to recognize an early phase of neurodegeneration.This study was supported by research grants:Slovak research and development agency APVV‐0677‐12 and VEGA 2/0147/16