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

Waragai, Masaaki; Ho, Gilbert; Takamatsu, Yoshiki; Sekiyama, Kazunari; Sugama, Shuei; Takenouchi, Takato; Masliah, Eliezer; Hashimoto, Makoto

doi:10.1002/acn3.436

Cited by 37 publications

(41 citation statements)

References 74 publications

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“…Adiponectin enhances AMPK activity via AdipoR1, and, in turn, AMPK activation represses amyloidogenesis, decreases mTOR signalling, and enhances autophagy and lysosomal degradation of beta-amyloid [28]. GSK-3β is recognised as another signalling molecule in adiponectin receptor signalling pathway [14]. It should be highlighted that GSK-β is involved in tau and beta-amyloid production [29], and it is regarded as a critical molecular link between two histopathological hallmarks of AD: senile plaques and neurofibrillary tangles [30].…”

Section: Discussionmentioning

confidence: 99%

Osoczowe stężenia frakcji adiponektyny u kobiet z chorobą Alzheimera

Baranowska-Bik¹,

Kalisz

Martyńska

et al. 2018

Endokrynologia Polska

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Introduction Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disease. Typical features of AD include memory loss, social dysfunction and physical impairment. Although the pathological findings in the central nervous system are well established, the etiological factors are poorly known. Recent studies suggested the role of metabolic disturbances in the development of AD neurodegeneration. Adiponectin, an anti-inflammatory and metabolism regulating factor, was linked to AD. Aim The aim was to examine whether adiponectin fractions combined with insulin/insulin resistance-associated metabolic parameters correlate with AD progression. Material and methods The study comprised 98 women: 27 with moderate to severe AD, 31 with AD at early stage and 40 healthy controls, matched for age and BMI. To evaluate memory impairment, the MMSE was performed. Plasma total adiponectin and its high-, medium- and low molecular weights were measured with ELISA. Anthropometric, clinical and metabolic parameters were assessed. Correlations between adiponectin array and measured parameters were evaluated. Results In comparison to the controls, enhanced levels of total and medium molecular weight adiponectin characterized AD individuals. In AD, we found correlations between adiponectin array, and anthropometric and biochemical parameters. After adjustment to BMI, a significant increase of the total adiponectin and high- and medium molecular weight fractions was observed. A negative correlation between low molecular weight adiponectin and MMSE was found. Conclusions Our results indicate a possible link between adiponectin variations and AD. We hypothesize that changes in adiponectin profile observed in AD result from compensatory mechanism against neuropathological processes, as well as from adiponectin homeostasis impairment.

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Section: Discussionmentioning

confidence: 99%

Osoczowe stężenia frakcji adiponektyny u kobiet z chorobą Alzheimera

Baranowska-Bik¹,

Kalisz

Martyńska

et al. 2018

Endokrynologia Polska

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“…Xu et al (2018) found that in the ICV-STZ rat model experiment, APN supplements inhibit hyperphosphorylation of tau protein at multiple AD-related sites, improve cognitive deficits, and have neuroprotective effects. But intriguingly, it is also reported that adaptation of APN to IR may play a dual role in the formation of two markers of AD: Aβ plaques and NFTs, and perhaps its fluctuation acts as a driving force in the disease pathogenesis (Sekiyama et al, 2014;Waragai et al, 2016Waragai et al, , 2017. Therefore, according to this unique biological mechanism of APN in AD, a selective therapeutic strategy that is distinct from previous concepts may be required.…”

Section: Inhibiting Hyperphosphorylation Of Tau In Nftsmentioning

confidence: 99%

Links Between Adiponectin and Dementia: From Risk Factors to Pathophysiology

Chen

Shu

Zeng

2020

Front. Aging Neurosci.

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With the aging population, dementia is becoming one of the most serious and troublesome global public health issues. Numerous studies have been seeking for effective strategies to delay or block its progression, but with little success. In recent years, adiponectin (APN) as one of the most abundant and multifunctional adipocytokines related to anti-inflammation, regulating glycogen metabolism and inhibiting insulin resistance (IR) and anti-atherosclerosis, has attracted widespread attention. In this article, we summarize recent studies that have contributed to a better understanding of the extent to which APN influences the risks of developing dementia as well as its pathophysiological progression. In addition, some controversial results interlinked with its effects on cognitive dysfunction diseases will be critically discussed. Ultimately, we aim to gain a novel insight into the pleiotropic effects of APN levels in circulation and suggest potential therapeutic target and future research strategies.

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“…In this regard, evolutionary biology might provide an effective viewpoint. We previously discussed that hyperadiponectinemia in AD might be a compensatory feedback to the decreased activity of insulin/IGF-1 receptor signaling pathway during the neurodegenerative conditions (1). As the disease progresses, APN might be increased and sequestered by tau, leading to neurotoxic protein aggregation in the brain of AD (1,8).…”

Section: Mechanism Of the Apn Paradox In Admentioning

confidence: 99%

“…We previously discussed that hyperadiponectinemia in AD might be a compensatory feedback to the decreased activity of insulin/IGF-1 receptor signaling pathway during the neurodegenerative conditions (1). As the disease progresses, APN might be increased and sequestered by tau, leading to neurotoxic protein aggregation in the brain of AD (1,8). An alternative and non-exclusive possibility is that misfolding of APN might downregulate the insulin/APN signal transduction network, resulting in the decrease of neurotrophic and neuroprotective activities.…”

Section: Mechanism Of the Apn Paradox In Admentioning

confidence: 99%

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Adiponectin Paradox in Alzheimer's Disease; Relevance to Amyloidogenic Evolvability?

Waragai

Ho²,

Takamatsu

et al. 2020

Front. Endocrinol.

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Adiponectin (APN) is a multi-functional adipokine which sensitizes the insulin signals, stimulates mitochondria biogenesis, and suppresses inflammation. By virtue of these beneficial properties, APN may protect against metabolic syndrome, including obesity and type II diabetes mellitus. Since these diseases are associated with hypoadiponectinemia, it is suggested that loss of function of APN might be involved. In contrast, despite beneficial properties for cardiovascular cells, APN is detrimental in circulatory diseases, including chronic heart failure (CHF) and chronic kidney disease (CKD). Notably, such an APN paradox might also be applicable to neurodegeneration. Although APN is neuroprotective in various experimental systems, APN was shown to be associated with the severity of amyloid accumulation and cognitive decline in a recent prospective cohort study in elderly. Furthermore, Alzheimer's disease (AD) was associated with hyperadiponectinemia in many studies. Moreover, APN was sequestered by phospho-tau into the neurofibrillary tangle in the postmortem AD brains. These results collectively indicate that APN might increase the risk of AD. In this context, the objective of the present study is to elucidate the mechanism of the APN paradox in AD. Hypothetically, APN might be involved in the stimulation of the amyloidogenic evolvability in reproductive stage, which may later manifest as AD by the antagonistic pleiotropy mechanism during aging. Given the accumulating evidence that AD and CHF are mechanistically overlapped, it is further proposed that the APN paradox of AD might be converged with those of other diseases, such as CHF and CKD.

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

Cited by 37 publications

References 74 publications

Osoczowe stężenia frakcji adiponektyny u kobiet z chorobą Alzheimera

Osoczowe stężenia frakcji adiponektyny u kobiet z chorobą Alzheimera

Links Between Adiponectin and Dementia: From Risk Factors to Pathophysiology

Adiponectin Paradox in Alzheimer's Disease; Relevance to Amyloidogenic Evolvability?

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