Eating peptides: biomarkers of neurodegeneration in amyotrophic lateral sclerosis and frontotemporal dementia

Objective Physiological changes potentially influence disease progression and survival along the Amyotrophic Lateral Sclerosis (ALS)-Frontotemporal dementia (FTD) spectrum. The peripheral peptides that regulate eating and metabolism may provide diagnostic, metabolic, and progression biomarkers. The current study aimed to examine the relationships and biomarker potential of hormonal peptides. Methods One hundred and twenty-seven participants (36 ALS, 26 ALS- cognitive, patients with additional cognitive behavioral features, and 35 behavioral variant FTD (bvFTD) and 30 controls) underwent fasting blood analyses of leptin, ghrelin, neuropeptide Y (NPY), peptide YY (PYY), and insulin levels. Relationships between endocrine measures, cognition, eating behaviors, and body mass index (BMI) were investigated. Biomarker potential was evaluated using multinomial logistic regression for diagnosis and correlation to disease duration. Results Compared to controls, ALS and ALS-cognitive had higher NPY levels and bvFTD had lower NPY levels, while leptin levels were increased in all patient groups. All groups had increased insulin levels and a state of insulin resistance compared to controls. Lower NPY levels correlated with increasing eating behavioral change and BMI, while leptin levels correlated with BMI. On multinomial logistic regression, NPY and leptin levels were found to differentiate between diagnosis. Reduced Neuropeptide Y levels correlated with increasing disease duration, suggesting it may be useful as a potential marker of disease progression. Interpretation ALS-FTD is characterized by changes in NPY and leptin levels that may impact on the underlying regional neurodegeneration as they were predictive of diagnosis and disease duration, offering the potential as biomarkers and for the development of interventional treatments.