Inflammatory hypothesis as a link between <scp>A</scp>lzheimer's disease and diabetes mellitus

Bozluolçay, Melda; Andican, Gülnur; Fırtına, Sinem; Erkol, Gökhan; Konukoğlu, Dildar

doi:10.1111/ggi.12602

Cited by 31 publications

(14 citation statements)

References 31 publications

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“…Traditionally, AD and DM have been considered two independent diseases. However, recent studies have shown that they share several pathophysiological mechanisms, including specific inflammatory signaling pathways (Bozluolcay et al, 2015), oxidative stress, and cell apoptosis. For example, in FIGURE 4 | Sirt1 expression in the brain.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective Effect of Resveratrol via Activation of Sirt1 Signaling in a Rat Model of Combined Diabetes and Alzheimer’s Disease

Sun

Han

et al. 2020

Front. Neurosci.

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Background: Alzheimer's disease (AD) and diabetes mellitus (DM) often coexist in patients because having one of these conditions increases risk for the other. These two diseases share several pathophysiological mechanisms, such as specific inflammatory signaling pathways, oxidative stress, and cell apoptosis. It is still unclear exactly which mechanisms associated with DM are responsible for increased AD risk. Studies have found that even transient elevation of brain Aβ levels can allow T2DM to slightly disrupt the neural milieu in a way that encourages pathologies associated with the onset of memory deficits and AD. A recent study argues that a potential common pathogenetic mechanism underlying both DM and AD is evidenced by the cooccurrence of amyloid brain legions and deposits containing both tau and Aβ in pancreatic β cells. Given these links, an investigation detailing disease mechanisms as well as treatment options for patients with cooccurring DM and AD is urgently needed. The biological effects of resveratrol relevant to DM and AD treatment include its abilities to modulate oxidative stress and reduce inflammation. A rat model of DM and concomitant AD was created for this study using intraperitoneal injection of streptozotocin and hippocampal injection of Aβ1-40 to characterize resveratrol's potential protective action. Results: Resveratrol significantly increased the Sirt1 expression, inhibited the memory impairment, the increased acetylcholinesterase, malondialdehyde, interleukin-1β and interleukin 6 levels, and the decreased levels of choline acetyltransferase (ChAT), superoxide dismutase (SOD), and glutathione in this rat model of diabetes and concomitant AD. The Sirt 1 inhibitor EX527 partially reversed the effects of resveratrol. Conclusion: This study suggests that resveratrol may have a neuroprotective action through activation of Sirt1 signaling in diabetes and AD with concurrent onset.

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Section: Discussionmentioning

confidence: 99%

Neuroprotective Effect of Resveratrol via Activation of Sirt1 Signaling in a Rat Model of Combined Diabetes and Alzheimer’s Disease

Sun

Han

et al. 2020

Front. Neurosci.

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“…Both AD and type 2 diabetes involve chronic inflammation and share similar pathological features including insulin resistance, hyperglycemia, and increased advanced glycation end-products. 58 Patients with type 2 diabetes have an increased risk of developing AD. 59 This is likely because impaired insulin signaling attenuates the production and function of insulindegrading enzyme in the brain, which might lead to inefficient Aβ clearance.…”

Section: Neuroinflammation In Ad Progressionmentioning

confidence: 99%

Section: Clinical Trials Of Drugs With Anti-inflammatory Effectsmentioning

confidence: 99%

Targeting Neuroinflammation as a Therapeutic Strategy for Alzheimer’s Disease: Mechanisms, Drug Candidates, and New Opportunities

Wang

2018

ACS Chem. Neurosci.

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Alzheimer's disease is a progressive neurodegenerative disease, and its incidence is expected to increase owing to the aging population worldwide. Current therapies merely provide symptomatic relief. Therefore, interventions for AD that delay the disease onset or progression are urgently required. Recent genomics and functional studies suggest that immune/inflammatory pathways are involved in the pathogenesis of AD. Although many anti-inflammatory drug candidates have undergone clinical trials, most have failed. This might be because of our limited understanding of the pathological mechanisms of neuroinflammation in AD. However, recent advances in the understanding of immune/inflammatory pathways in AD and their regulatory mechanisms could open up new avenues for drug development targeting neuroinflammation. In this Review, we discuss the mechanisms and status of different anti-inflammatory drug candidates for AD that have undergone or are undergoing clinical trials and explore new opportunities for targeting neuroinflammation in AD drug development.

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“…101 Both medial temporal lobe atrophy 98,99 and hippocampal volumes 102 with cerebral SVD are associated with conversion to AD or the other subtypes of dementia in MCI patients. Atrial fibrillation and diabetes could also be a risk factor for AD and VaD, 103,104 in addition to stroke. 105 These results support the notion that individuals with vascular pathologies have increased odds of dementia compared with individuals with a single pathology.…”

Section: Cognitive Impairmentmentioning

confidence: 99%

White matter hyperintensities and geriatric syndrome: An important role of arterial stiffness

Saji

Ogama

Toba

et al. 2015

Geriatrics Gerontology Int

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White matter hyperintensities (WMH) are defined as cerebral white matter changes presumed to be of vascular origin, bilateral and mostly symmetrical. They can appear as hyperintense on T2-weighted and fluid-attenuated inversion recovery sequences, and as isointense or hypointense on T1-weighted magnetic resonance imaging of the brain. WMH have been focused on because of their clinical importance as a risk factor for cerebrovascular diseases and cognitive impairment. WMH are associated with geriatric syndrome, which is defined by clinical symptoms characteristic of older adults, including cognitive and functional impairment and falls. Cerebral small vessel diseases, such as WMH, might play an important role as risk factors for cerebrovascular diseases, cognitive impairment and geriatric syndrome through the mechanism of arterial stiffness. However, the vascular, physiological and metabolic roles of arterial stiffness remain unclear. Basically, arterial stiffness indicates microvessel arteriosclerosis presenting with vascular endothelial dysfunction. These changes might arise from hemodynamic stress as a result of a "tsunami effect" on cerebral parenchyma. In the present article, we review the clinical characteristics of WMH, focusing particularly on two associations: (i) those between cerebral small vessel diseases including WMH and arterial stiffness; and (ii) those between WMH and geriatric syndrome. Geriatr Gerontol Int 2015; 15 (Suppl. 1): 17-25.

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Inflammatory hypothesis as a link between Alzheimer's disease and diabetes mellitus

Abstract: Our findings support the presence of a low-grade systemic inflammation link between AD and DM. Geriatr Gerontol Int 2016; 16: 1161-1166.

Cited by 31 publications

References 31 publications

Neuroprotective Effect of Resveratrol via Activation of Sirt1 Signaling in a Rat Model of Combined Diabetes and Alzheimer’s Disease

Neuroprotective Effect of Resveratrol via Activation of Sirt1 Signaling in a Rat Model of Combined Diabetes and Alzheimer’s Disease

Targeting Neuroinflammation as a Therapeutic Strategy for Alzheimer’s Disease: Mechanisms, Drug Candidates, and New Opportunities

White matter hyperintensities and geriatric syndrome: An important role of arterial stiffness

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