Altered Serum Levels of Adipokines and Insulin in Probable Alzheimer's Disease

Khemka, Vineet Kumar; Bagchi, Debajit; Bandyopadhyay, Kausik; Bir, Aritri; Chattopadhyay, Matangini; Biswas, Atanu; Basu, Debasis; Chakrabarti, Sasanka

doi:10.3233/jad-140006

Cited by 92 publications

(80 citation statements)

References 58 publications

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“…Consistent with previous studies [7][8][9][10], serum APN levels in MCI and AD were significantly higher than in controls. A large-scale study in 2012 showed that increased plasma APN was an independent risk factor for development of all-cause dementia and AD in women [7].…”

Section: Discussionsupporting

confidence: 80%

“…Previous clinical studies have shown that lifestyle-related diseases such as hypertension, type II diabetes, dyslipidemia, and obesity may enhance the risks for AD and other neurodegenerative diseases [7][8][9][10]. However, only one study has examined APN in this context, with Une et al finding increased serum APN in patients with mild cognitive impairment (MCI) and AD compared to age-matched normal controls (NC) and increased CSF APN in MCI compared to NC [8].…”

Section: Introductionmentioning

confidence: 92%

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Possible Involvement of Adiponectin, the Anti-Diabetes Molecule, in the Pathogenesis of Alzheimer’s Disease

Waragai

Adame

Trinh

et al. 2016

JAD

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Abstract. Adiponectin (APN) is protective in animal models of neurodegenerative diseases, but the role of APN in human brain has not been established. Using an enzyme-linked immunosorbent assay, we found that APN was significantly decreased in cerebrospinal fluid (CSF) of patients with Alzheimer's disease (AD), compared to those in patients with mild cognitive impairment (MCI) and in normal controls (NC), despite elevation of APN in serum of patients with MCI and AD compared to that in NC. The discrepancy of CSF APN from serum APN in AD may suggest some critical actions of APN in the pathogenesis of AD. Indeed, it was histologically observed that APN was co-localized with tau in neurofibrillary tangles and immunoblot analysis showed that the functional trimers of APN were significantly decreased in AD compared to those in NC. Collectively, a loss of function of APN may be involved in the pathogenesis of AD.

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Section: Discussionsupporting

confidence: 80%

Section: Introductionmentioning

confidence: 92%

Possible Involvement of Adiponectin, the Anti-Diabetes Molecule, in the Pathogenesis of Alzheimer’s Disease

Waragai

Adame

Trinh

et al. 2016

JAD

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“…Increased levels of plasma APN in AD were confirmed by Khemka et al,11 Waragai et al.,12 and Ma et al 13,. but Warren et al 34.…”

Section: Apn May Increase Ad Riskmentioning

confidence: 63%

“…1). 9, 10, 11, 12, 13 More recently, increased levels of plasma APN were found to be associated with the burden of amyloid deposits and degree of cognitive impairment in a prospective cohort study for the elderly,14 also suggesting that APN may instead promote neurodegeneration in AD.…”

Section: Introductionmentioning

confidence: 99%

Importance of adiponectin activity in the pathogenesis of Alzheimer's disease

Waragai

Ho²,

Takamatsu

et al. 2017

Ann Clin Transl Neurol

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A recent study suggested that insulin resistance may play a central role in the pathogenesis of Alzheimer's disease (AD). In this regard, it is of note that upregulation of plasma adiponectin (APN), a benign adipokine that sensitizes the insulin receptor signaling pathway and suppresses inflammation, has recently been associated with the severities of amyloid deposits and cognitive deficits in the elderly, suggesting that APN may enhance the risk of AD. These results are unanticipated because AD has been linked to type II diabetes and other metabolic disorders in which hypoadiponectinemia has been firmly established, and because APN ameliorated neuropathological features in a mouse model of neurodegeneration. Therefore, the objective of this study is to discuss the possible mechanisms underlying the biological actions of APN in the context of AD. Given that insulin receptor signaling is required for normal function of the nervous system, we predict that APN may be upregulated to compensate for compromised activity of the insulin receptor signaling pathway. However, increased APN might be sequestered by tau in the brain, leading to neurotoxic protein aggregation in AD. Alternatively, misfolding of APN may result in downregulation of the insulin/APN signal transduction network, leading to decreased neuroprotective and neurotrophic activities. Thus, it is possible that both ‘gain of function’ and ‘loss of function’ of APN may underlie synaptic dysfunction and neuronal cell death in AD. Such a unique biological mechanism underlying APN function in AD may require a novel therapeutic strategy that is distinct from previous treatment for metabolic disorders.

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“…The metabolic implications of AD pathogenesis in the context of brain insulin deficiency and insulin resistance have been extensively discussed in several recent publications [45,46]. Although multiple causes have been attributed to altered food intake and loss of body weight in AD, the fact also implies a role of hormones like insulin and adipokines in its pathogenesis [48,49,50]. The mitochondrial dysfunction and inhibition of key metabolic enzymes involved in energy production like the glycolytic enzymes as also pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, cytochrome oxidase are established features of AD pathology indicating general metabolic perturbation in brain in this condition [50,51].…”

Section: Metabolic and Endocrine Components In Ad Pathogenesismentioning

confidence: 99%

Metabolic Risk Factors of Sporadic Alzheimer's Disease: Implications in the Pathology, Pathogenesis and Treatment

Chakrabarti¹,

Khemka²,

Banerjee³

et al. 2015

Aging and disease

Self Cite

107

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Alzheimer's disease (AD), the major cause of dementia among the elderly world-wide, manifests in familial and sporadic forms, and the latter variety accounts for the majority of the patients affected by this disease. The etiopathogenesis of sporadic AD is complex and uncertain. The autopsy studies of AD brain have provided limited understanding of the antemortem pathogenesis of the disease. Experimental AD research with transgenic animal or various cell based models has so far failed to explain the complex and varied spectrum of AD dementia. The review, therefore, emphasizes the importance of AD related risk factors, especially those with metabolic implications, identified from various epidemiological studies, in providing clues to the pathogenesis of this complex disorder. Several metabolic risk factors of AD like hypercholesterolemia, hyperhomocysteinemia and type 2 diabetes have been studied extensively both in epidemiology and experimental research, while much less is known about the role of adipokines, proinflammatory cytokines and vitamin D in this context. Moreover, the results from many of these studies have shown a degree of variability which has hindered our understanding of the role of AD related risk factors in the disease progression. The review also encompasses the recent recommendations regarding clinical and neuropathological diagnosis of AD and brings out the inherent uncertainty and ambiguity in this area which may have a distinct impact on the outcome of various population-based studies on AD-related risk factors.

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Altered Serum Levels of Adipokines and Insulin in Probable Alzheimer's Disease

Cited by 92 publications

References 58 publications

Possible Involvement of Adiponectin, the Anti-Diabetes Molecule, in the Pathogenesis of Alzheimer’s Disease

Possible Involvement of Adiponectin, the Anti-Diabetes Molecule, in the Pathogenesis of Alzheimer’s Disease

Importance of adiponectin activity in the pathogenesis of Alzheimer's disease

Metabolic Risk Factors of Sporadic Alzheimer's Disease: Implications in the Pathology, Pathogenesis and Treatment

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