Adiponectin: The Potential Regulator and Therapeutic Target of Obesity and Alzheimer’s Disease

Abstract

Animal and human mechanistic studies have consistently shown an association between obesity and Alzheimer’s disease (AD). AD, a degenerative brain disease, is the most common cause of dementia and is characterized by the presence of extracellular amyloid beta (Aβ) plaques and intracellular neurofibrillary tangles disposition. Some studies have recently demonstrated that Aβ and tau cannot fully explain the pathophysiological development of AD and that metabolic disease factors, such as insulin, adiponectin, and antioxidants, are important for the sporadic onset of nongenetic AD. Obesity prevention and treatment can be an efficacious and safe approach to AD prevention. Adiponectin is a benign adipokine that sensitizes the insulin receptor signaling pathway and suppresses inflammation. It has been shown to be inversely correlated with adipose tissue dysfunction and may enhance the risk of AD because a range of neuroprotection adiponectin mechanisms is related to AD pathology alleviation. In this study, we summarize the recent progress that addresses the beneficial effects and potential mechanisms of adiponectin in AD. Furthermore, we review recent studies on the diverse medications of adiponectin that could possibly be related to AD treatment, with a focus on their association with adiponectin. A better understanding of the neuroprotection roles of adiponectin will help clarify the precise underlying mechanism of AD development and progression.

A Fundamental Role for Oxidants and Intracellular Calcium Signals in Alzheimer’s Pathogenesis—And How a Comprehensive Antioxidant Strategy May Aid Prevention of This Disorder

“…Improved cerebrovascular health, diminished microglial inflammation, heat shock protein induction, increased production of neurotropic factors systemically and in the brain, and episodic exposure to lactic acid have been postulated as possible mediators of the protection from AD afforded by regular vigorous exercise [ 282 , 283 , 284 , 285 , 286 , 287 ]. Elevated levels of the “longevity hormone” fibroblast growth factor 21 (FGF21) and of adiponectin might help to explain the lower risk for AD observed in long-term vegans and quasi-vegan societies, as these hormones are protective in mouse AD models [ 288 , 289 , 290 , 291 , 292 , 293 , 294 ]. Strikingly, the Ibadan-Indianapolis Dementia Project, a longitudinal study following elderly African-Americans in Indianapolis and elderly Africans in Ibadan during the 1990s, and using standardized diagnostic criteria, found that age-adjusted incidence of AD was less than half as high in the latter group [ 295 ].…”

Neurotrophic factor levels in the serum and cerebrospinal fluid of neonates infected with human cytomegalovirus

“…Acrp30, a cytokine derived from the regulation and secretion of insulin by fat cells, is involved in fat and carbohydrate metabolism and the coordination of brain function 22,23 . This adipokine ameliorates the pathological changes of Alzheimer's disease by regulating the function of microglia 24 .…”

NM101 Phase III Study of NE3107 in Alzheimer’s Disease: rationale, Design and Therapeutic Modulation of Neuroinflammation and Insulin Resistance

“…CRP is not only an inflammatory biomarker, it facilitates complement and immune activation, and tissue damage in AD [27]. Increased HDL is reported to decrease AD risk [28], and increased adiponectin sensitizes the insulin receptor signaling pathway, suppresses inflammation, and is neuroprotective against AD pathology [29].…”