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

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

doi:10.1111/acel.12281

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

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

Research output: Contribution to journal › Article › peer-review

63 Citations (Scopus)

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.

Original language	English
Number of pages	8
Journal	AGING CELL
Early online date	2 Dec 2014
DOIs	https://doi.org/10.1111/acel.12281
Publication status	Published - 2014

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Maioli, S., Lodeiro, M., Merino-Serrais, P., Falahati, F., Khan, W., Puerta, E., Codita, A., Rimondini, R., Ramirez, M. J., Simmons, A., Gil-Bea, F., Westman, E., Cedazo-Minguez, A., & the Alzheimer's Disease Neuroimaging Initiative (2014). Alterations in brain leptin signalling in spite of unchanged CSF leptin levels in Alzheimer's disease. AGING CELL. https://doi.org/10.1111/acel.12281

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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.",

author = "Silvia Maioli and Maria Lodeiro and Paula Merino-Serrais and Farshad Falahati and Wasim Khan and Elena Puerta and Alina Codita and Roberto Rimondini and Ramirez, {Maria J} and Andrew Simmons and Francisco Gil-Bea and Eric Westman and Angel Cedazo-Minguez and {the Alzheimer's Disease Neuroimaging Initiative}",

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doi = "10.1111/acel.12281",

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Maioli, S, Lodeiro, M, Merino-Serrais, P, Falahati, F, Khan, W, Puerta, E, Codita, A, Rimondini, R, Ramirez, MJ, Simmons, A, Gil-Bea, F, Westman, E, Cedazo-Minguez, A & the Alzheimer's Disease Neuroimaging Initiative 2014, 'Alterations in brain leptin signalling in spite of unchanged CSF leptin levels in Alzheimer's disease', AGING CELL. https://doi.org/10.1111/acel.12281

TY - JOUR

T1 - Alterations in brain leptin signalling in spite of unchanged CSF leptin levels in Alzheimer's disease

AU - Maioli, Silvia

AU - Lodeiro, Maria

AU - Merino-Serrais, Paula

AU - Falahati, Farshad

AU - Khan, Wasim

AU - Puerta, Elena

AU - Codita, Alina

AU - Rimondini, Roberto

AU - Ramirez, Maria J

AU - Simmons, Andrew

AU - Gil-Bea, Francisco

AU - Westman, Eric

AU - Cedazo-Minguez, Angel

AU - the Alzheimer's Disease Neuroimaging Initiative

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

U2 - 10.1111/acel.12281

DO - 10.1111/acel.12281

M3 - Article

C2 - 25453257

SN - 1474-9718

JO - AGING CELL

JF - AGING CELL

ER -

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

Abstract

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