Impact of Genetic Risk Factors for Alzheimer’s Disease on Brain Glucose Metabolism

Cho, Sukhee; Lee, Hyein; Seo, Jinsoo

doi:10.1007/s12035-021-02297-x

Cited by 17 publications

(12 citation statements)

References 120 publications

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“…In fact, insulin is an enhancer of memory performance and this effect is likely to be associated with its positive influence on brain synaptic plasticity, neuronal glucose uptake and neuropathological consequences of AD [ 51 ]. After all, the beneficial activity of intranasal insulin may be closely related to the normalization of dysfunctional glucose metabolism, which probably results from genetic risk factors in AD patients [ 180 ]. In addition, some antidepressant drugs (citalopram, escitalopram) were shown to be clinically beneficial in at least some aspects of AD patients.…”

Section: Discussionmentioning

confidence: 99%

Some Candidate Drugs for Pharmacotherapy of Alzheimer’s Disease

Miziak

Błaszczyk²,

Czuczwar

2021

Pharmaceuticals

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Alzheimer’s disease (AD; progressive neurodegenerative disorder) is associated with cognitive and functional impairment with accompanying neuropsychiatric symptoms. The available pharmacological treatment is of a symptomatic nature and, as such, it does not modify the cause of AD. The currently used drugs to enhance cognition include an N-methyl-d-aspartate receptor antagonist (memantine) and cholinesterase inhibitors. The PUBMED, Medical Subject Heading and Clinical Trials databases were used for searching relevant data. Novel treatments are focused on already approved drugs for other conditions and also searching for innovative drugs encompassing investigational compounds. Among the approved drugs, we investigated, are intranasal insulin (and other antidiabetic drugs: liraglitude, pioglitazone and metformin), bexarotene (an anti-cancer drug and a retinoid X receptor agonist) or antidepressant drugs (citalopram, escitalopram, sertraline, mirtazapine). The latter, especially when combined with antipsychotics (for instance quetiapine or risperidone), were shown to reduce neuropsychiatric symptoms in AD patients. The former enhanced cognition. Procognitive effects may be also expected with dietary antioxidative and anti-inflammatory supplements—curcumin, myricetin, and resveratrol. Considering a close relationship between brain ischemia and AD, they may also reduce post-brain ischemia neurodegeneration. An investigational compound, CN-105 (a lipoprotein E agonist), has a very good profile in AD preclinical studies, and its clinical trial for postoperative dementia is starting soon.

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Section: Discussionmentioning

confidence: 99%

Some Candidate Drugs for Pharmacotherapy of Alzheimer’s Disease

Miziak

Błaszczyk²,

Czuczwar

2021

Pharmaceuticals

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“…(2010) have shown that the CH25H gene plays a key role in AD susceptibility. Recent large genome‐wide association studies (GWASs) have found that genetic variations in genes NEDD9, SORCS1, DAPK1, PICALM, and PRNP are related to AD risk (Bagyinszky et al., 2019; Cho et al., 2021; Hermey et al., 2019; Xu et al., 2015, 2019), evaluating SNPs on the above genes helps to determine AD progression.…”

Section: Real Data Analysismentioning

confidence: 99%

“…Recent large genome-wide association studies (GWASs) have found that genetic variations in genes NEDD9, SORCS1, DAPK1, PICALM, and PRNP TA B L E 5 Frequency of scalar predictors selected at 0.1, 0.5, and 0.9 quantiles across 1000 bootstrap. are related to AD risk (Bagyinszky et al, 2019;Cho et al, 2021;Hermey et al, 2019;Xu et al, 2015Xu et al, , 2019, evaluating SNPs on the above genes helps to determine AD progression.…”

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confidence: 99%

Smoothed quantile regression for partially functional linear models in high dimensions

et al. 2023

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Practitioners of current data analysis are regularly confronted with the situation where the heavy‐tailed skewed response is related to both multiple functional predictors and high‐dimensional scalar covariates. We propose a new class of partially functional penalized convolution‐type smoothed quantile regression to characterize the conditional quantile level between a scalar response and predictors of both functional and scalar types. The new approach overcomes the lack of smoothness and severe convexity of the standard quantile empirical loss, considerably improving the computing efficiency of partially functional quantile regression. We investigate a folded concave penalized estimator for simultaneous variable selection and estimation by the modified local adaptive majorize‐minimization (LAMM) algorithm. The functional predictors can be dense or sparse and are approximated by the principal component basis. Under mild conditions, the consistency and oracle properties of the resulting estimators are established. Simulation studies demonstrate a competitive performance against the partially functional standard penalized quantile regression. A real application using Alzheimer's Disease Neuroimaging Initiative data is utilized to illustrate the practicality of the proposed model.

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“…Emerging evidence from both human and animal studies underscores a significant association between obesity and cognitive decline, including brain atrophy, diminished white matter volume, compromised blood–brain barrier integrity, and heightened susceptibility to late-onset Alzheimer's disease [ [1] , [2] , [3] , [4] , [5] , [6] ]. Furthermore, chronic disruptions in glucose homeostasis, impaired insulin signaling, and metabolic dysfunctions are closely linked to cognitive impairments and the pathology of Alzheimer's disease [ [7] , [8] , [9] , [10] , [11] , [12] , [13] ]. These observations suggest the importance of maintaining normal body weight and proper fuel metabolism, which is crucial to reducing the risk of developing cognitive decline and neurodegenerative diseases.…”

Section: Introductionmentioning

confidence: 99%

LRP1 in GABAergic neurons is a key link between obesity and memory function

da Cruz Rodrigues,

Kim,

Uner

et al. 2024

Molecular Metabolism

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Impact of Genetic Risk Factors for Alzheimer’s Disease on Brain Glucose Metabolism

Cited by 17 publications

References 120 publications

Some Candidate Drugs for Pharmacotherapy of Alzheimer’s Disease

Some Candidate Drugs for Pharmacotherapy of Alzheimer’s Disease

Smoothed quantile regression for partially functional linear models in high dimensions

LRP1 in GABAergic neurons is a key link between obesity and memory function

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