Alterations in brain leptin signalling in spite of unchanged CSF leptin levels in Alzheimer's disease

Aging Cell

Silvia Maioli¹  Maria Lodeiro¹  Paula Merino-Serrais¹  Farshad Falahati⁴  Wasim Khan³  Elena Puerta¹  Alina Codita¹  Roberto Rimondini⁵  Maria J. Ramirez⁶  Andrew Simmons³  Francisco Gil-Bea²  Eric Westman⁴  Angel Cedazo-Minguez¹ 

[1] Karolinska Institutet, Department of Neurobiology Care Sciences and Society, Center for Alzheimer Research, Division for Neurogeriatrics, Stockholm, Sweden;Department of Cellular and Molecular Neuropharmacology, Division of Neurosciences, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain;Institute of Psychiatry, King's College London, London, UK;Karolinska Institutet Department of Neurobiology Care Sciences and Society, Center for Alzheimer Research, Division for clinical geriatrics, Stockholm, Sweden;Medical and Surgical Science, Department-DIMEC-University of Bologna, Bologna, Italy;Department of Pharmacology and Toxicology, University of Navarra, Pamplona, Spain

关键词: Alzheimer's disease;    amyloid‐beta;    ApoE genotype;    CSF;    leptin receptors;    leptin;   

DOI  :  10.1111/acel.12281

来源: Wiley

【 摘 要 】

Summary

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 Aβ_1-42. 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.

【 授权许可】

CC BY   
© 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

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