Significant association of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) rs3846662 and sirtuin 1 (SIRT1) rs7895833 and apolipoprotein E (APOE) hypermethylation with mild cognitive impairment (MCI)

Zou, Ting; Duan, Ying; Zhou, Xiaohui; Chen, Wei; Ying, Xiuru; Liu, Guili; Zhao, Yan; Zhu, Meisheng; Pari, Abuliz; Alimu, Kader; Miao, Heng; Kabinur, Keyim; Zhang, Lei; Wang, Qinwen; Duan, Shiwei

doi:10.1097/md.0000000000016405

Cited by 3 publications

(3 citation statements)

References 41 publications

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“…Remarkably, alterations in brain structure are restricted to AD neuropathological regions and occur before the clinical onset of AD [ 88 ]. Regarding the three clinical phases (NC, MCI, and AD), HMGCR mainly acts during the MCI stage, where it may also impact brain glucose metabolism [ 89 , 90 ] and contribute to the pathophysiological transition from MCI to AD [ 90 , 91 ]. When the rat hypothalamus is injected with HMGCR inhibitors, this not only alters insulin signaling and lipid storage metabolism via mevalonate channels but also increases the neuronal activity of the arcuate nucleus and the paraventricular nucleus (PVN) [ 92 ].…”

Section: Hmgcr As a Therapeutic Target For Admentioning

confidence: 99%

Mechanisms of 3-Hydroxyl 3-Methylglutaryl CoA Reductase in Alzheimer’s Disease

Zhou,

Wu,

Wang

et al. 2023

IJMS

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Alzheimer’s disease (AD) is the most common neurodegenerative disease worldwide and has a high incidence in the elderly. Unfortunately, there is no effective therapy for AD owing to its complicated pathogenesis. However, the development of lipid-lowering anti-inflammatory drugs has heralded a new era in the treatment of Alzheimer’s disease. Several studies in recent years have shown that lipid metabolic dysregulation and neuroinflammation are associated with the pathogenesis of AD. 3-Hydroxyl 3-methylglutaryl CoA reductase (HMGCR) is a rate-limiting enzyme in cholesterol synthesis that plays a key role in cholesterol metabolism. HMGCR inhibitors, known as statins, have changed from being solely lipid-lowering agents to neuroprotective compounds because of their effects on lipid levels and inflammation. In this review, we first summarize the main regulatory mechanism of HMGCR affecting cholesterol biosynthesis. We also discuss the pathogenesis of AD induced by HMGCR, including disordered lipid metabolism, oxidative stress, inflammation, microglial proliferation, and amyloid-β (Aβ) deposition. Subsequently, we explain the possibility of HMGCR as a potential target for AD treatment. Statins-based AD treatment is an ascent field and currently quite controversial; therefore, we also elaborate on the current application prospects and limitations of statins in AD treatment.

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Section: Hmgcr As a Therapeutic Target For Admentioning

confidence: 99%

Mechanisms of 3-Hydroxyl 3-Methylglutaryl CoA Reductase in Alzheimer’s Disease

Zhou,

Wu,

Wang

et al. 2023

IJMS

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“…127 Another SNP in the HMGCR gene is rs3846662, which was shown to affect MCI in females regardless of ApoE4. 128 This same SNP might also be protective like HMGCR's rs3846662 G negative status in French Canadians, which delayed the onset of AD by 3.6 years and so modified the risk of AD and also decreased the conversion rate from MCI to AD. 129 Additionally, Northern Han Chinese population was at reduced risk of LOAD when presenting with the minor A allele at rs3846662 of the HMGCR gene in APOE4 non-carriers.…”

Section: Hyperlipidemiamentioning

confidence: 99%

“…Swedish people, for example, do not exhibit an increase in AD risk if they have this SNP, regardless of whether they carry the ApoE4 allele or not 127 . Another SNP in the HMGCR gene is rs3846662, which was shown to affect MCI in females regardless of ApoE4 128 . This same SNP might also be protective like HMGCR's rs3846662 G negative status in French Canadians, which delayed the onset of AD by 3.6 years and so modified the risk of AD and also decreased the conversion rate from MCI to AD 129 .…”

Section: Modifiable Risk Factors Of Admentioning

confidence: 99%

Precision health in Alzheimer disease: Risk assessment‐based strategies

Azar

Salama

Chidambaram

et al. 2021

Precision Medical Sciences

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Alzheimer disease (AD) is a chronic neurodegenerative condition that affects an individual's cognitive function over an extended period. Treatment and prevention for AD have long been sought after; however, no strategy has yet been successful, as individuals with cognitive impairment usually present to the clinic when they have reached an advanced stage of the disease. The disease is progressive and multifactorial in its pathogenesis. Precision medicine (PM) is the new era of medicine comprising a holistic approach in dealing with diseases. With scientific innovations, PM has improved our disease knowledge, altered diagnoses and therapy approaches resulting in a more precise, predictive, preventative and personalized patient care. PM in AD focuses, among other things, on stratifying individuals according to their risk factors of developing the disease and applying preventative strategies and personalized treatment approaches for a better outcome. In this mini‐review, we have focused on a few modifiable and non‐modifiable risk factors and presented recommendations for future consideration to implement.

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Sirtuins and aging

Morris

2021

Sirtuin Biology in Medicine

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Significant association of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) rs3846662 and sirtuin 1 (SIRT1) rs7895833 and apolipoprotein E (APOE) hypermethylation with mild cognitive impairment (MCI)

Abstract: Supplemental Digital Content is available in the text

Cited by 3 publications

References 41 publications

Mechanisms of 3-Hydroxyl 3-Methylglutaryl CoA Reductase in Alzheimer’s Disease

Mechanisms of 3-Hydroxyl 3-Methylglutaryl CoA Reductase in Alzheimer’s Disease

Precision health in Alzheimer disease: Risk assessment‐based strategies

Sirtuins and aging

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