Does metabolic syndrome impact cognition and emotion in <scp>A</scp>lzheimer's disease?

Willette, Auriel A.

doi:10.1111/ene.12879

Cited by 3 publications

(3 citation statements)

References 9 publications

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“…The identification of several metabolic networks, including lipid and amino acid metabolism, and metabolic pathways involved in glucose and energy substrate utilization provides insights into potential disease mechanism and therapeutic targets. These findings together with the identification of additional risk factors for AD, such as type 2 diabetes, strengthen the notion that AD is a metabolic disorder ( 196 – 200 ). Metabolomics profiling coupled to pathway analysis could aid in the understanding of the underlying disease mechanisms leading to the development of novel blood-based biomarkers for the diagnosis, prognosis, and monitoring therapeutic efficacy.…”

Section: Discussionsupporting

confidence: 70%

Application of Metabolomics in Alzheimer’s Disease

2018

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Progress toward the development of efficacious therapies for Alzheimer’s disease (AD) is halted by a lack of understanding early underlying pathological mechanisms. Systems biology encompasses several techniques including genomics, epigenomics, transcriptomics, proteomics, and metabolomics. Metabolomics is the newest omics platform that offers great potential for the diagnosis and prognosis of neurodegenerative diseases as an individual’s metabolome reflects alterations in genetic, transcript, and protein profiles and influences from the environment. Advancements in the field of metabolomics have demonstrated the complexity of dynamic changes associated with AD progression underscoring challenges with the development of efficacious therapeutic interventions. Defining systems-level alterations in AD could provide insights into disease mechanisms, reveal sex-specific changes, advance the development of biomarker panels, and aid in monitoring therapeutic efficacy, which should advance individualized medicine. Since metabolic pathways are largely conserved between species, metabolomics could improve the translation of preclinical research conducted in animal models of AD into humans. A summary of recent developments in the application of metabolomics to advance the AD field is provided below.

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Section: Discussionsupporting

confidence: 70%

Application of Metabolomics in Alzheimer’s Disease

2018

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“…This oxidative stress is further compounded by inflammatory processes associated with alterations in cellular metabolism [ 24 , 30 , 31 ]. Type 2 diabetes mellitus (T2DM) confers an additional risk factor for AD [ 32 - 36 ], suggesting that deranged metabolism contributes to AD development [ 11 , 37 , 38 ]. Several recent studies demonstrate epigenetic modifications in aging and neurodegeneration.…”

Section: Introductionmentioning

confidence: 99%

Mitochondrially-Targeted Therapeutic Strategies for Alzheimer’s Disease

Onyango

Bennett

Stokin

2021

CAR

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: Alzheimer's disease (AD) is an irreversible, progressive neurodegenerative disease and the most common cause of dementia among older adults. There are no effective treatments avail- able for the disease, and it is associated with great societal concern because of the substantial costs of providing care to its sufferers, whose numbers will increase as populations age. While multiple causes have been proposed to be significant contributors to the onset of sporadic AD, increased age is a unifying risk factor. In addition to amyloid-β (Aβ) and tau protein playing a key role in the initi- ation and progression of AD, impaired mitochondrial bioenergetics and dynamics are likely major etiological factors in AD pathogenesis and have many potential origins, including Aβ and tau. Mito- chondrial dysfunction is evident in the central nervous system (CNS) and systemically early in the disease process. Addressing these multiple mitochondrial deficiencies is a major challenge of mito- chondrial systems biology. We review evidence for mitochondrial impairments ranging from mito- chondrial DNA (mtDNA) mutations to epigenetic modification of mtDNA, altered gene expres- sion, impaired mitobiogenesis, oxidative stress, altered protein turnover and changed organelle dy- namics (fission and fusion). We also discuss therapeutic approaches, including repurposed drugs, epigenetic modifiers, and lifestyle changes that target each level of deficiency which could poten- tially alter the course of this progressive, heterogeneous Disease while being cognizant that success- ful future therapeutics may require a combinatorial approach.

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“…The neurodegenerative diseases constitute major economic and social as well as medical challenges . The association of dementia with income, mortality, morbidity and medication use has been highlighted with a study from Denmark , with effects seen years before diagnosis.…”

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confidence: 99%