Interpretation of risk loci from genome-wide association studies of Alzheimer's disease

Andrews, Shea J.; Fulton‐Howard, Brian; Goate, Alison

doi:10.1016/s1474-4422(19)30435-1

Cited by 260 publications

(268 citation statements)

References 35 publications

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“…Aging is a key risk factor for AD. Despite the long lifespan of people with AD, they suffer prolonged disability out of the dramatic progress of the disease and a variety of other aging-related comorbidities [ 25 , 60 , 65 ]. As illustrated before, AD pathology may result from other existing metabolic and hormonal dysregulations such as hyperlipidemia, obesity, type 2 diabetes mellitus, hypertension and other cardiovascular disorders, as well as severely decreased levels of sex steroids [ 5 , 13 , 54 , 58 ].…”

Section: Discussionmentioning

confidence: 99%

“…AD patients experience other neuropsychiatric problems such as mood dysregulation and depressive symptoms, especially during the prodromal stage [ 25 ]. RJ may alleviate the depression that cooccurs in AD.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to cognitive deterioration, the main characteristic symptom of AD, numerous other symptoms develop such as language disturbances, functional impairments in ADL, and a wide range of neuropsychiatric symptoms, e.g., depression, irritability, anxiety, agitation, apathy/indifference, delusions, and hallucinations. Evidence indicates that depression and irritability represent early AD symptoms that exist alongside MCI before AD diagnosis [ 25 ]. The course of the disease begins with mild symptoms that gradually get more severe [ 26 ].…”

Section: Overview Of Alzheimer’s Diseasementioning

confidence: 99%

“…The course of the disease begins with mild symptoms that gradually get more severe [ 26 ]. Symptoms associated with AD heighten caregivers’ burden and increase rates of institutionalization and mortality [ 25 ].…”

Section: Overview Of Alzheimer’s Diseasementioning

confidence: 99%

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Royal Jelly as an Intelligent Anti-Aging Agent—A Focus on Cognitive Aging and Alzheimer’s Disease: A Review

Ali

2020

Antioxidants

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The astronomical increase of the world’s aged population is associated with the increased prevalence of neurodegenerative diseases, heightened disability, and extremely high costs of care. Alzheimer’s Disease (AD) is a widespread, age-related, multifactorial neurodegenerative disease that has enormous social and financial drawbacks worldwide. The unsatisfactory outcomes of available AD pharmacotherapy necessitate the search for alternative natural resources that can target various the underlying mechanisms of AD pathology and reduce disease occurrence and/or progression. Royal jelly (RJ) is the main food of bee queens; it contributes to their fertility, long lifespan, and memory performance. It represents a potent nutraceutical with various pharmacological properties, and has been used in a number of preclinical studies to target AD and age-related cognitive deterioration. To understand the mechanisms through which RJ affects cognitive performance both in natural aging and AD, we reviewed the literature, elaborating on the metabolic, molecular, and cellular mechanisms that mediate its anti-AD effects. Preclinical findings revealed that RJ acts as a multidomain cognitive enhancer that can restore cognitive performance in aged and AD models. It promotes brain cell survival and function by targeting multiple adversities in the neuronal microenvironment such as inflammation, oxidative stress, mitochondrial alterations, impaired proteostasis, amyloid-β toxicity, Ca excitotoxicity, and bioenergetic challenges. Human trials using RJ in AD are limited in quantity and quality. Here, the limitations of RJ-based treatment strategies are discussed, and directions for future studies examining the effect of RJ in cognitively impaired subjects are noted.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Overview Of Alzheimer’s Diseasementioning

confidence: 99%

Section: Overview Of Alzheimer’s Diseasementioning

confidence: 99%

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Royal Jelly as an Intelligent Anti-Aging Agent—A Focus on Cognitive Aging and Alzheimer’s Disease: A Review

Ali

2020

Antioxidants

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“…Furthermore, many sporadic AD patients are carriers of the e4 allele of the ApoE gene (apolipoprotein E; chromosome 19) [47]. In addition, today, the genome-wide association studies of AD are nearing identification of a wide range of genetic loci influencing the risk of AD [48]. Regarding other tauopathies, the cases with the mutated tau gene (FTDP-17) [38] make up a substantial fraction of those with corticobasal degeneration or frontotemporal dementia [26].…”

Section: Genetic Factorsmentioning

confidence: 99%

Xenobiotics, Trace Metals and Genetics in the Pathogenesis of Tauopathies

Aaseth

Buha

Wallace

et al. 2020

IJERPH

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Tauopathies are a disease group characterized by either pathological accumulation or release of fragments of hyperphosphorylated tau proteins originating from the central nervous system. The tau hypotheses of Parkinson’s and Alzheimer’s diseases contain a clinically diverse spectrum of tauopathies. Studies of case records of various tauopathies may reveal clinical phenotype characteristics of the disease. In addition, improved understanding of different tauopathies would disclose environmental factors, such as xenobiotics and trace metals, that can precipitate or modify the progression of the disorder. Important for diagnostics and monitoring of these disorders is a further development of adequate biomarkers, including refined neuroimaging, or proteomics. Our goal is to provide an in-depth review of the current literature regarding the pathophysiological roles of tau proteins and the pathogenic factors leading to various tauopathies, with the perspective of future advances in potential therapeutic strategies.

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Delivering the Promise of Gene Therapy with Nanomedicines in Treating Central Nervous System Diseases

et al. 2022

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Central Nervous System (CNS) diseases, such as Alzheimer's diseases (AD), Parkinson's Diseases (PD), brain tumors, Huntington's disease (HD), and stroke, still remain difficult to treat by the conventional molecular drugs. In recent years, various gene therapies have come into the spotlight as versatile therapeutics providing the potential to prevent and treat these diseases. Despite the significant progress that has undoubtedly been achieved in terms of the design and modification of genetic modulators with desired potency and minimized unwanted immune responses, the efficient and safe in vivo delivery of gene therapies still poses major translational challenges. Various non‐viral nanomedicines have been recently explored to circumvent this limitation. In this review, an overview of gene therapies for CNS diseases is provided and describes recent advances in the development of nanomedicines, including their unique characteristics, chemical modifications, bioconjugations, and the specific applications that those nanomedicines are harnessed to deliver gene therapies.

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Interpretation of risk loci from genome-wide association studies of Alzheimer's disease

Cited by 260 publications

References 35 publications

Royal Jelly as an Intelligent Anti-Aging Agent—A Focus on Cognitive Aging and Alzheimer’s Disease: A Review

Royal Jelly as an Intelligent Anti-Aging Agent—A Focus on Cognitive Aging and Alzheimer’s Disease: A Review

Xenobiotics, Trace Metals and Genetics in the Pathogenesis of Tauopathies

Delivering the Promise of Gene Therapy with Nanomedicines in Treating Central Nervous System Diseases

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