Open AccessAlterations in brain leptin signalling in spite of unchanged CSF leptin levels in Alzheimer's disease
Author(s) -
Maioli Silvia,
Lodeiro Maria,
MerinoSerrais Paula,
Falahati Farshad,
Khan Wasim,
Puerta Elena,
Codita Alina,
Rimondini Roberto,
Ramirez Maria J.,
Simmons Andrew,
GilBea Francisco,
Westman Eric,
CedazoMinguez Angel
Publication year - 2015
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12281
Subject(s) - leptin , disease , signalling , biology , alzheimer's disease , medicine , endocrinology , neuroscience , obesity , microbiology and biotechnology
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.