Adiponectin and sporadic Alzheimer's disease: Clinical and molecular links

Obesity has been consistently associated with Alzheimer's disease (AD) though the exact mechanisms by which it influences cognition are still elusive and subject of current research. Adiponectin, the most abundant adipokine in circulation, is inversely correlated with adipose tissue dysfunction and seems to be a central player in this association. In fact, different signalling pathways are shared by adiponectin and proteins involved in AD pathophysiology and considerable amount of evidence supports its direct and indirect influence on beta-amyloid and tau aggregates formation. In this paper we present a critical review of cellular, animal and clinical studies which have contributed to a more thorough understanding of the extent to which adiponectin influences the risk of developing AD as well as its progression. Finally, the effect of acetylcholinesterase inhibitors on circulating adiponectin levels, possible therapeutic applications and future research strategies are also discussed.