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Dietary Neuroketotherapeutics for Alzheimer's Disease: An Evidence Update and the Potential Role for Diet Quality.

ABSTRACT: Alzheimer's disease (AD) is a devastating neurodegenerative disease with growing prevalence as the global population ages. Currently available treatments for AD have minimal efficacy and there are no proven treatments for its prodrome, mild cognitive impairment (MCI). AD etiology is not well understood and various hypotheses of disease pathogenesis are currently under investigation. A consistent hallmark in patients with AD is reduced brain glucose utilization; however, evidence suggests that brain ketone metabolism remains unimpaired, thus, there is a great deal of increased interest in the potential value of ketone-inducing therapies for the treatment of AD (neuroketotherapeutics; NKT). The goal of this review was to discuss dietary NKT approaches and mechanisms by which they exert a possible therapeutic benefit, update the evidence available on NKTs in AD and consider a potential role of diet quality in the clinical use of dietary NKTs. Whether NKTs affect AD symptoms through the restoration of bioenergetics, the direct and indirect modulation of antioxidant and inflammation pathways, or both, preliminary positive evidence suggests that further study of dietary NKTs as a disease-modifying treatment in AD is warranted.

SUBMITTER: Taylor MK

PROVIDER: S-EPMC6722814 | biostudies-other | 2019 Aug

REPOSITORIES: biostudies-other

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Dietary Neuroketotherapeutics for Alzheimer's Disease: An Evidence Update and the Potential Role for Diet Quality.

Taylor Matthew K MK Swerdlow Russell H RH Sullivan Debra K DK

Nutrients 20190815 8

Alzheimer's disease (AD) is a devastating neurodegenerative disease with growing prevalence as the global population ages. Currently available treatments for AD have minimal efficacy and there are no proven treatments for its prodrome, mild cognitive impairment (MCI). AD etiology is not well understood and various hypotheses of disease pathogenesis are currently under investigation. A consistent hallmark in patients with AD is reduced brain glucose utilization; however, evidence suggests that br ...[more]

PMID: 31443216

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Project description:A non-invasive and early-detectable peripheral biomarker is urgently needed for Alzheimer's disease (AD). The present study is a step forward to verify the biomarker properties of human microRNA-455-3p (Hsa-miR-455-3p) in AD patients. Our previous findings on mild cognitive impaired subjects, AD patients and AD cells and mouse models unveiled the miR-455-3p as a potential peripheral biomarker for AD. In the current study, we verified the differential expression of miR-455-3p in postmortem AD brains obtained from NIH NeuroBioBank, and fibroblasts and B-lymphocytes from both familial and sporadic AD patients from Coriell Cell Repository of National Institutes on Aging. Total RNA was extracted from the fibroblasts, B-lymphocytes and AD postmortem brains, and expression of miR-455-3p was measured by real-time reverse-transcriptase RT-PCR. Our real-time RT-PCR analysis showed a significant (P = 0.0002) upregulation of miR-455-3p expression in AD postmortem brains compared to healthy control samples. Expression of miR-455-3p was also upregulated in the fibroblasts from AD patients, however a significant difference in miR-455-3p level was observed in the cells from sporadic AD patients (P = 0.014) compared to healthy controls. Similarly, in B-lymphocytes, miR-455-3p level was also higher (P = 0.044) especially in sporadic AD cases compared to controls. Receiver operating characteristic (ROC) curve analysis indicated the significant area under ROC curve (AUROC) value of miR-455-3p in AD postmortem brain (AUROC = 0.792; P = 0.001) and AD fibroblasts cells (AUROC = 0.861; P = 0.03), whereas in B-lymphocytes AUROC value of miR-455-3p was not significant. Further, in-silico analysis for miRNA targets predictions showed the binding capacity of miR-455-3p with several AD associated key genes such as APP, NGF, USP25, PDRG1, SMAD4, UBQLN1, SMAD2, TP73, VAMP2, HSPBAP1, and NRXN1. Hence, these observations further revealed that miR-455-3p is a potential biomarker for AD and its possible therapeutic target for AD.

Dataset Information

Dietary Neuroketotherapeutics for Alzheimer's Disease: An Evidence Update and the Potential Role for Diet Quality.

Publications

Dietary Neuroketotherapeutics for Alzheimer's Disease: An Evidence Update and the Potential Role for Diet Quality.

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