Biomarkers for Insulin Resistance and Inflammation and the Risk for All-Cause Dementia and Alzheimer Disease

Himbergen, Thomas M. van; Beiser, Alexa; Ai, Masumi; Seshadri, Sudha; Otokozawa, Seiko; Au, Rhoda; Thongtang, Nuntakorn; Wolf, Philip A.; Schaefer, Ernst J.

doi:10.1001/archneurol.2011.670

Cited by 180 publications

(157 citation statements)

References 47 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]. Gender may be a critical factor in the role of APN in the pathogenesis of AD, but we did not find a gender difference in changes of APN in AD (data not shown).…”

Section: Discussionsupporting

confidence: 92%

“…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: 99%

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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: 92%

Section: Introductionmentioning

confidence: 99%

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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“…Notably, the result of the Mayo Clinic study is consistent with those of the Framingham Heart Study, in which increased plasma APN levels were an independent risk factor for development of both all‐cause dementia and AD in women, but not in men 10, 14. One may predict that the gender difference of the association of APN with AD may be attributed to a hormonal difference, as APN and estrogen are inversely correlated and APN is increased in postmenopausal women 14, 43.…”

Section: Apn May Increase Ad Risksupporting

confidence: 76%

“…Consistent with these findings, the Framingham Heart Study undertook a prospective study of the contribution of biomarkers related to glucose homeostasis and inflammation to the risk of developing AD and all‐cause dementia in 840 dementia‐free participants (541 women and 299 men with a mean age of 72 years) showed that elevated APN was a predictor for all‐cause dementia and AD (Table 1). 10 Notably, the increase in plasma APN in AD was significant in women, but not in men 10…”

Section: Apn May Increase Ad Riskmentioning

confidence: 98%

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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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Inflammation in Alzheimer's Disease, and Prevention with Antioxidants and Phenolic Compounds – What Are the Most Promising Candidates?

Sharman

Verdile

Kirubakaran

et al. 2019

Neurodegeneration and Alzheimer's Disease

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Biomarkers for Insulin Resistance and Inflammation and the Risk for All-Cause Dementia and Alzheimer Disease

Cited by 180 publications

References 47 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

Inflammation in Alzheimer's Disease, and Prevention with Antioxidants and Phenolic Compounds – What Are the Most Promising Candidates?

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