Alterations in brain leptin signalling in spite of unchanged CSF leptin levels in Alzheimer's disease |
| |
| Authors: | Silvia Maioli Maria Lodeiro Paula Merino‐Serrais Farshad Falahati Wasim Khan Elena Puerta Alina Codita Roberto Rimondini Maria J Ramirez Andrew Simmons Francisco Gil‐Bea Eric Westman Angel Cedazo‐Minguez the Alzheimer's Disease Neuroimaging Initiative |
| |
| Institution: | 1. Karolinska Institutet, Department of Neurobiology Care Sciences and Society, Center for Alzheimer Research, Division for Neurogeriatrics, Stockholm, Sweden;2. Karolinska Institutet Department of Neurobiology Care Sciences and Society, Center for Alzheimer Research, Division for clinical geriatrics, Stockholm, Sweden;3. Institute of Psychiatry, King's College London, London, UK;4. Medical and Surgical Science, Department‐DIMEC‐University of Bologna, Bologna, Italy;5. Department of Pharmacology and Toxicology, University of Navarra, Pamplona, Spain;6. NIHR Biomedical Research, Centre for Mental Health, King's College London, London, UK;7. NIHR Biomedical Research, Unit for Dementia, King's College London, London, UK;8. Department of Cellular and Molecular Neuropharmacology, Division of Neurosciences, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain |
| |
| Abstract: | Several studies support the relation between leptin and Alzheimer's disease (AD). We show that leptin levels in CSF are unchanged as subjects progress to AD. However, in AD hippocampus, leptin signalling was decreased and leptin localization was shifted, being more abundant in reactive astrocytes and less in neurons. Similar translocation of leptin was found in brains from Tg2576 and apoE4 mice. Moreover, an enhancement of leptin receptors was found in hippocampus of young Tg2576 mice and in primary astrocytes and neurons treated with Aβ1‐42. In contrast, old Tg2576 mice showed decreased leptin receptors levels. Similar findings to those seen in Tg2576 mice were found in apoE4, but not in apoE3 mice. These results suggest that leptin levels are intact, but leptin signalling is impaired in AD. Thus, Aβ accumulation and apoE4 genotype result in a transient enhancement of leptin signalling that might lead to a leptin resistance state over time. |
| |
| Keywords: | Alzheimer's disease amyloid‐beta ApoE genotype
CSF
leptin receptors leptin |
|
|
