Background: Several studies have highlighted the contribution of adipose tissue dysfunction to the development and progression of Alzheimers Disease (AD), which may depend on alterations in adipokine secretion. Leptin and adiponectin are the most abundant adipokines in circulation, with recognized systemic effects, but also able to cross the blood-brain barrier and influence cognitive-related structures, such as the hippocampus.
Objective: To determine if serum and CSF adiponectin and leptin/adiponectin ratio are correlated with AD biomarkers and can constitute predictors of progression.
Methods: A total of 53 AD and 71 aMCI subjects (mild cognitive impairment amnestic type) were included and underwent a thorough clinical and neuropsychological evaluation (MMSE, MoCA, ADAS-Cog). Serum and CSF adiponectin and leptin, serum insulin and AD biomarkers (CSF Aβ42, t-tau, p-tau and hippocampal formation volumetry) were also performed. Sixty-seven MCI patients had clinical and neuropsychological follow-up in order to identify progression to AD.
Results: Serum adiponectin was 33% higher in AD when compared to MCI. In CSF, leptin and t-tau showed a negative correlation in AD patients (ρ=−0.597, P=0.026) while adiponectin was positively correlated with Aβ42 (ρ=0.590, P=0.002), but only in women. A robust association between CSF adiponectin and hippocampal volume was observed in a subgroup of patients with CSF-based AD diagnosis. However, no correlation was found with total cognitive scores. Twenty-seven MCI progressed to AD upon a mean follow-up of 38.2±18.83 months, whereas 40 maintained the diagnosis. Baseline serum and CSF adipokine levels were similar in both groups. Only serum adiponectin positively correlated with time of progression (ρ=0.484, P=0.049), though incapable of predicting progression to dementia.
Conclusions: Higher CSF adiponectin levels are associated with less Aβ42 deposition and higher hippocampal volume. Accordingly, higher adiponectinemia observed in AD could be looked as a strategy to maintain its central levels and, consequently, its beneficial effects.
20 May 2017 - 23 May 2017