Plasma Leptin Reflects Progression of Neurofibrillary Pathology in Animal Model of Tauopathy

The close relationship between Alzheimer's disease (AD) and obesity was recognized many years ago. However, complete understanding of the pathological mechanisms underlying the interactions between degeneration of CNS and fat metabolism is still missing. The leptin a key adipokine of white adipose tissue has been suggested as one of the major mediators linking the obesity and AD. Here we investigated the association between peripheral levels of leptin, general metabolic status and stage of the pathogenesis in rat transgenic model of AD. We demonstrate significantly decreased levels of plasma leptin in animals with experimentally induced progressive neurofibrillary pathology, which represents only 62.3% (P = 0.0015) of those observed in normal wild type control animals. More detailed analysis showed a strong and statistically significant inverse correlation between the load of neurofibrillary pathology and peripheral levels of leptin (r = - 0.7248,P = 0.0177). We also observed a loss of body weight during development of neurodegeneration (about 14% less than control animals,P = 0.0004) and decrease in several metabolic parameters such as glucose, insulin, triglycerides and VLDL in plasma of the transgenic animals. Our data suggest that plasma leptin could serve as a convenient peripheral biomarker for tauopathies and Alzheimer's disease. Decrease in gene expression of leptin in fat tissue and its plasma level was found as one of the consequences of experimentally induced neurodegeneration. Our data may help to design rational diagnostic and therapeutic strategies for patients suffering from Alzheimer's disease or other forms of tauopathy.

Automated summary

The close relationship between Alzheimer's disease and obesity, mediated by the key adipokine leptin, was investigated in rat transgenic model. The study found decreased levels of plasma leptin and body weight, as well as a correlation between neurofibrillary pathology and leptin levels. The data suggests that plasma leptin could serve as a convenient biomarker for tauopathies and Alzheimer's disease.