scholarly journals Betahydroxybutyrate Consumption in Autopsy Brain Tissue from Alzheimer’s Disease Subjects

2021 ◽  
Vol 5 (1) ◽  
pp. 135-141
Author(s):  
Russell H. Swerdlow ◽  
Mony J. de Leon ◽  
David L. Marcus
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glucose Utilization ◽  
Ketone Bodies ◽  
Temporal Cortex ◽  
Co2 Production ◽  
Utilization Rate ◽  
Brain Glucose ◽  
Autopsy Brain Tissue ◽  
Brain Glucose Utilization

Background: Alzheimer’s disease (AD) features perturbed brain glucose utilization, which could contribute to brain bioenergetic failure. This led some to consider using ketone bodies to enhance AD brain bioenergetics and treat AD. Objective: We evaluated the rate at which brain homogenates from persons with Alzheimer’s disease (AD) metabolize D-β-hydroxybutyrate (BHB). Methods: We homogenized pieces of temporal cortex from frozen autopsy brains obtained from recently deceased AD subjects (n = 4), and age-matched subjects that did not have clinical AD (n = 3). Measuring the rate of CO2 production that followed the introduction of radiolabeled BHB to the homogenates yielded a BHB utilization rate. Results: Compared to the control homogenates, the BHB-supported CO2 production rate was 66%lower in the AD homogenates (p < 0.05). Conclusions: AD brains can utilize BHB, albeit less robustly than control brains. In conjunction with a previous study that demonstrated reduced glucose utilization in AD brain homogenates, our BHB data provide further evidence of AD brain mitochondrial dysfunction or altered mitochondrial biology.

P2-126: Inactivation of a key mitochondrial protein may lead to reduced brain glucose utilization in Alzheimer's disease

2012 ◽  
Vol 8 (4S_Part_8) ◽  
pp. P304-P304
Author(s):  
Gary Gibson ◽  
Hui Xu ◽  
Qingli Shi ◽  
Vahram Haroutunian ◽  
Yuling Chen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glucose Utilization ◽  
Mitochondrial Protein ◽  
Brain Glucose ◽  
Brain Glucose Utilization

O2-07-05: Investigations of brain glucose utilization in three transgenic mouse strains that develop neuropathological features of Alzheimer's disease

2013 ◽  
Vol 9 ◽  
pp. P329-P329 ◽  
Author(s):  
Jonathan Kelley ◽  
Cindy Wintmolders ◽  
Astrid Bottelbergs ◽  
Ann-Mari Waldron ◽  
Leonie Wyffels ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mouse ◽  
Glucose Utilization ◽  
Mouse Strains ◽  
Brain Glucose ◽  
Brain Glucose Utilization

scholarly journals A Dietary Ketone Ester Normalizes Abnormal Behavior in a Mouse Model of Alzheimer’s Disease

2020 ◽  
Vol 21 (3) ◽  
pp. 1044
Author(s):  
Robert J. Pawlosky ◽  
Yoshihero Kashiwaya ◽  
M. Todd King ◽  
Richard L. Veech
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Tca Cycle ◽  
Abnormal Behavior ◽  
Control Group ◽  
Brain Glucose ◽  
Model Of Alzheimer’S Disease ◽  
Brain Glucose Utilization ◽  
Ketone Ester

Because of a decreased sensitivity toward insulin, a key regulator of pyruvate dehydrogenase (PDH), Alzheimer’s patients have lower brain glucose utilization with reductions in Tricarboxylic Acid (TCA) cycle metabolites such as citrate, a precursor to n-acetyl-aspartate. In the 3xTgAd mouse model of Alzheimer’s disease (AD), aging mice also demonstrate low brain glucose metabolism. Ketone metabolism can overcome PDH inhibition and restore TCA cycle metabolites, thereby enhancing amino acid biosynthesis. A ketone ester of d-β-hydroxybutyrate was incorporated into a diet (Ket) and fed to 3xTgAd mice. A control group was fed a calorically matched diet (Cho). At 15 months of age, the exploratory and avoidance-related behavior patterns of the mice were evaluated. At 16.5 months of age, the animals were euthanized, and their hippocampi were analyzed for citrate, α-ketoglutarate, and amino acids. In the hippocampi of the Ket-fed mice, there were higher concentrations of citrate and α-ketoglutarate as well as higher concentrations of glutamate, aspartate and n-acetyl-aspartate compared with controls. There were positive associations between (1) concentrations of aspartate and n-acetyl-aspartate (n = 14, R = 0.9327), and (2) α-ketoglutarate and glutamate (n = 14, R = 0.8521) in animals maintained on either diet. Hippocampal n-acetyl-aspartate predicted the outcome of several exploratory and avoidance-related behaviors. Ketosis restored citrate and α-ketoglutarate in the hippocampi of aging mice. Higher concentrations of n-acetyl-aspartate corresponded with greater exploratory activity and reduced avoidance-related behavior.

scholarly journals Dietary Neuroketotherapeutics for Alzheimer’s Disease: An Evidence Update and the Potential Role for Diet Quality

Nutrients ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1910 ◽  
Author(s):  
Matthew K. Taylor ◽  
Russell H. Swerdlow ◽  
Debra K. Sullivan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Diet Quality ◽  
Potential Role ◽  
Glucose Utilization ◽  
Therapeutic Benefit ◽  
Disease Modifying Treatment ◽  
Global Population ◽  
Brain Glucose Utilization

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.

Alzheimer’s Disease

2016 ◽  
Author(s):  
Richard L. Veech ◽  
M. Todd King
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pyruvate Dehydrogenase ◽  
Glucose Utilization ◽  
Ketone Bodies ◽  
Krebs Cycle ◽  
Cerebral Glucose Utilization ◽  
And Function ◽  
Promising Avenue ◽  
Brain Energetics

Deficits in cerebral glucose utilization in Alzheimer’s disease (AD) arise decades before cognitive impairment and accumulation of amyloid plaques and neurofibrillary tangles in brain. Addressing this metabolic deficit has greater potential in treating AD than targeting later disease processes – an approach that has failed consistently in the clinic. Cerebral glucose utilization requires numerous enzymes, many of which have been shown to decline in AD. Perhaps the most important is pyruvate dehydrogenase (PDH), which links glycolysis with the Krebs cycle and aerobic metabolism, and whose activity is greatly suppressed in AD. The unique metabolism of ketone bodies allows them to bypass the block at pyruvate dehydrogenase and restore brain metabolism. Recent studies in mouse genetic models of AD and in a human Alzheimer’s patient showed the potential of ketones in maintaining brain energetics and function. Oral ketone bodies might be a promising avenue for treatment of Alzheimer’s disease.

Reduction in Brain Glucose Utilization Rate after Tryptophol (3-Indole Ethanol) Treatment

1981 ◽  
Vol 36 (5) ◽  
pp. 1758-1765 ◽  
Author(s):  
Eain M. Cornford ◽  
Paul D. Crane ◽  
Leon D. Braun ◽  
William D. Bocash ◽  
Anthony M. Nyerges ◽  
...  
Keyword(s):  
Glucose Utilization ◽  
Utilization Rate ◽  
Ethanol Treatment ◽  
Brain Glucose ◽  
Brain Glucose Utilization

scholarly journals Tau isoforms are differentially expressed across the hippocampus in chronic traumatic encephalopathy and Alzheimer’s disease

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Jonathan D. Cherry ◽  
Camille D. Esnault ◽  
Zachary H. Baucom ◽  
Yorghos Tripodis ◽  
Bertrand R. Huber ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Chronic Traumatic Encephalopathy ◽  
Temporal Cortex ◽  
Head Impacts ◽  
Hippocampal Subfields ◽  
Mild Disease ◽  
Tau Isoforms ◽  
Ghost Tangles

AbstractChronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease, characterized by hyperphosphorylated tau, found in individuals with a history of exposure to repetitive head impacts. While the neuropathologic hallmark of CTE is found in the cortex, hippocampal tau has proven to be an important neuropathologic feature to examine the extent of disease severity. However, the hippocampus is also heavily affected in many other tauopathies, such as Alzheimer’s disease (AD). How CTE and AD differentially affect the hippocampus is unclear. Using immunofluorescent analysis, a detailed histologic characterization of 3R and 4R tau isoforms and their differential accumulation in the temporal cortex in CTE and AD was performed. CTE and AD were both observed to contain mixed 3R and 4R tau isoforms, with 4R predominating in mild disease and 3R increasing proportionally as pathological severity increased. CTE demonstrated high levels of tau in hippocampal subfields CA2 and CA3 compared to CA1. There were also low levels of tau in the subiculum compared to CA1 in CTE. In contrast, AD had higher levels of tau in CA1 and subiculum compared to CA2/3. Direct comparison of the tau burden between AD and CTE demonstrated that CTE had higher tau densities in CA4 and CA2/3, while AD had elevated tau in the subiculum. Amyloid beta pathology did not contribute to tau isoform levels. Finally, it was demonstrated that higher levels of 3R tau correlated to more severe extracellular tau (ghost tangles) pathology. These findings suggest that mixed 3R/4R tauopathies begin as 4R predominant then transition to 3R predominant as pathological severity increases and ghost tangles develop. Overall, this work demonstrates that the relative deposition of tau isoforms among hippocampal subfields can aid in differential diagnosis of AD and CTE, and might help improve specificity of biomarkers for in vivo diagnosis.

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