Adiponectin levels in the serum and cerebrospinal fluid of amyotrophic lateral sclerosis patients: possible influence on neuroinflammation?

Patrizia Bossolasco,Alberto Doretti,Vincenzo Silani,Claudia Morelli,Lidia Cova,Raffaella Cancello

doi:10.1186/s12974-017-0861-2

Abstract

BackgroundAdiponectin (APN) is a key player in energy homeostasis strictly associated with cerebrovascular and neurodegenerative diseases. Since APN also belongs to anti-inflammatory-acting adipokines and may influence both neuroinflammation and neurodegenerative processes, we decided to study the APN levels in amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases.MethodsWe assessed APN levels by ELISA immunoassay in both the serum and cerebrospinal fluid of a cohort of familial and sporadic ALS patients, characterized by normal body mass index and absence of dysautonomic symptoms. The screening of serum APN levels was also performed in patients affected by other neurological disorders, including fronto-temporal dementia (FTD) patients. Means were compared using the non-parametric Wilcoxon test, and Pearson’s or Spearman’s rho was used to assess correlations between variables.ResultsIn the whole ALS group, serum APN levels were not different when compared to the age- and sex-matched control group (CTR), but a gender-specific analysis enlightened a significant opposite APN trend between ALS males, characterized by lower values (ALS 9.8 ± 5.2 vs. CTR 15 ± 9.7 μg/ml), and ALS females, showing higher amounts (ALS 26.5 ± 11.6 vs. CTR 14.6 ± 5.2 μg/ml). This sex-linked difference was significantly enhanced in familial ALS cases (p ≤ 0.01). The APN levels in ALS cerebrospinal fluids were unrelated to serum values and not linked to sex and/or familiarity of the disease. Finally, the screening of serum APN levels in patients affected by other neurological disorders revealed the highest serum values in FTD patients.ConclusionsOpposite serum APN levels are gender-related in ALS and altered in several neurological disorders, with the highest values in FTD, which shares with ALS several overlapping and neuropathological features. Further investigations are needed to clarify the possible involvement of APN in neuroinflammation and neurodegeneration.Graphical Possible involvement of APN in neuroinflammatory neurodegenerative diseases

Highlights

Adiponectin (APN) is a key player in energy homeostasis strictly associated with cerebrovascular and neurodegenerative diseases
Characteristics of amyotrophic lateral sclerosis (ALS) patients vs. control group (CTR) The whole group of ALS patients was comparable to CTR for all the considered parameters, except for glutamic oxaloacetic transaminase/aspartate aminotransferase (GOT (AST)) and glutamate-pyruvate transaminase 1/alanine aminotransferase (GPT (ALT)) levels, which were significantly increased (p < 0.05, Table 1)
ALS males were characterized by significantly different values for glutamatepyruvate transaminase 1/alanine aminotransferase (ALT) and AST in comparison to CTR, as for the whole group, whereas in female ALS, only total cholesterol levels were slightly increased

Summary

Introduction

Adiponectin (APN) is a key player in energy homeostasis strictly associated with cerebrovascular and neurodegenerative diseases. Increased levels of APN may be viewed as a rescue mechanism to counteract the ongoing neuronal loss, even if dual and opposite effects of APN on neuroinflammation, oxidative stress and neuronal apoptosis have been reported [2, 3, 7,8,9,10,11]. In this controversial scenario, the APN impact on different neurological conditions remains undefined, as well as the eventual ability of APN subforms to cross the bloodbrain barrier (BBB) [3]. Higher serum APN values have been associated with neuroimaging markers of neurodegeneration and cognitive impairment among women in the Mayo Clinic Study of Aging [6]

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