title: Alterations in brain leptin signalling in spite of unchanged CSF leptin levels in Alzheimer's disease.
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.
authors.affiliation: Karolinska Institutet, Department of Neurobiology Care Sciences and Society, Center for Alzheimer Research, Division for Neurogeriatrics, Stockholm, Sweden.
authors.forename: Silvia
authors.initials: S
authors.lastname: Maioli
authors.forename: Maria
authors.initials: M
authors.lastname: Lodeiro
authors.forename: Paula
authors.initials: P
authors.lastname: Merino-Serrais
authors.forename: Farshad
authors.initials: F
authors.lastname: Falahati
authors.forename: Wasim
authors.initials: W
authors.lastname: Khan
authors.forename: Elena
authors.initials: E
authors.lastname: Puerta
authors.forename: Alina
authors.initials: A
authors.lastname: Codita
authors.forename: Roberto
authors.initials: R
authors.lastname: Rimondini
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Ramirez
authors.forename: Andrew
authors.initials: A
authors.lastname: Simmons
authors.forename: Francisco
authors.initials: F
authors.lastname: Gil-Bea
authors.forename: Eric
authors.initials: E
authors.lastname: Westman
authors.forename: Angel
authors.initials: A
authors.lastname: Cedazo-Minguez
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000473:pathology; D000818:Animals; D053327:Apolipoprotein E4 / Q000235:genetics; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D020738:Leptin / Q000134:cerebrospinal fluid*; D016014:Linear Models; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D059906:Neuroimaging; D009929:Organ Size; D054411:Receptors, Leptin / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D053327:Apolipoprotein E4; D015415:Biomarkers; D020738:Leptin; D054411:Receptors, Leptin
keywords: Alzheimer's disease; ApoE genotype; CSF; amyloid-beta; leptin; leptin receptors