scholarly journals Methyl-Beta-Cyclodextrin Restores KIR Channel Function in Brain Endothelium of Female Alzheimer’s Disease Mice

2021 ◽  
Vol 5 (1) ◽  
pp. 693-703
Author(s):  
Md A. Hakim ◽  
Erik J. Behringer

Background: As the sixth-leading cause of death in the United States, Alzheimer’s disease (AD) entails deteriorating endothelial control of blood flow throughout the brain. In particular, reduced inward-rectifying K+ (KIR) channel function in animal models of aging and AD compromises endothelial function and optimal perfusion of brain parenchyma. Deficient endothelial KIR channels may result from aberrant interaction with plasma membrane cholesterol as a primary regulator of membrane fluidity and ion channels. Objective: We tested the hypothesis that mild methyl-β-cyclodextrin (MβCD) treatment to reduce membrane cholesterol may restore endothelial KIR channel function in brain endothelium of old AD mice. Methods: Membrane potential was continuously measured in isolated endothelial tubes from posterior cerebral arteries of young (1 to 3 months) and old (16 to 19 months) female 3xTg-AD mice before and after mild treatment with the cholesterol-removing agent MβCD (1 mmol/L). Elevated extracellular potassium ([K+]E; 15 mmol/L) and NS309 (1μmol/L) activated KIR and Ca2+-activated K+ (SKCa/IKCa) channels respectively before and after MβCD treatment. Results: SKCa/IKCa channel function for producing hyperpolarization remained stable regardless of age group and MβCD treatment (ΔVm: ∼–33 mV). However, as deficient during AD, KIR channel function was restored (ΔVm: –9±1 mV) versus pre-MβCD conditions (–5±1 mV); a progressive effect that reached –14±1 mV hyperpolarization at 60 min following MβCD washout. Conclusion: In female animals, MβCD treatment of brain endothelium selectively restores KIR versus SKCa/IKCa channel function during AD. Thus, the endothelial cholesterol-KIR channel interface is a novel target for ameliorating perfusion of the AD brain.

2008 ◽  
Vol 9 (1) ◽  
pp. 4-10 ◽  
Author(s):  
Robin C. Fenley ◽  
Sarah J. Bober ◽  
Mebane E. Powell ◽  
Jacquelin Berman ◽  
Barbara N. Altman

This article reports on the first 2 years of an ongoing project that examined the efficacy of a 10-hour dementia training provided to entry-level personal care aide (PCA) trainees from the Hispanic, White, African American, and Asian communities in New York City. Participants were enrolled in a 90-hour PCA training program offered by the New York City Department for the Aging and were either recipients of public assistance, displaced employees from September 11, or recent immigrants to the United States from China. Classes were conducted in Spanish, English, and Mandarin/Cantonese. An 11-item Knowledge of Alzheimer’s Disease instrument was developed for the purposes of this project and administered before and after the dementia training and at 3 months following graduation. All groups, regardless of language, showed a significant increase in knowledge of Alzheimer’s disease at the conclusion of the training and retention of this knowledge at 3 months follow-up. Age was strongly correlated with an increase in knowledge, while gender and education were not.


2019 ◽  
Author(s):  
Clemens Kruse ◽  
Britney Larson ◽  
Reagan Wilkinson ◽  
Roger Samson ◽  
Taylor Castillo

BACKGROUND Incidence of AD continues to increase, making it the most common cause of dementia and the sixth-leading cause of death in the United States. 2018 numbers are expected to double by 2030. OBJECTIVE We examined the benefits of utilizing technology to identify and detect Alzheimer’s disease in the diagnostic process. METHODS We searched PubMed and CINAHL using key terms and filters to identify 30 articles for review. We analyzed these articles and reported them in accordance with the PRISMA guidelines. RESULTS We identified 11 technologies used in the detection of Alzheimer’s disease: 66% of which used some form of MIR. Functional, structural, and 7T magnetic resonance imaging were all used with structural being the most prevalent. CONCLUSIONS MRI is the best form of current technology being used in the detection of Alzheimer’s disease. MRI is a noninvasive approach that provides highly accurate results in the diagnostic process of Alzheimer’s disease.


2020 ◽  
Vol 300 ◽  
pp. 221-225 ◽  
Author(s):  
Mai Vu ◽  
Marjaana Koponen ◽  
Heidi Taipale ◽  
Antti Tanskanen ◽  
Jari Tiihonen ◽  
...  

1996 ◽  
Vol 17 (4) ◽  
pp. S95
Author(s):  
L. Hebert ◽  
P. Scherr ◽  
L. Beckett ◽  
D. Evans

2010 ◽  
Vol 30 (11) ◽  
pp. 1883-1889 ◽  
Author(s):  
Allyson R Zazulia ◽  
Tom O Videen ◽  
John C Morris ◽  
William J Powers

Studies in transgenic mice overexpressing amyloid precursor protein (APP) demonstrate impaired autoregulation of cerebral blood flow (CBF) to changes in arterial pressure and suggest that cerebrovascular dysfunction may be critically important in the development of pathological Alzheimer's disease (AD). Given the relevance of such a finding for guiding hypertension treatment in the elderly, we assessed autoregulation in individuals with AD. Twenty persons aged 75±6 years with very mild or mild symptomatic AD (Clinical Dementia Rating 0.5 or 1.0) underwent 15O-positron emission tomography (PET) CBF measurements before and after mean arterial pressure (MAP) was lowered from 107±13 to 92±9 mm Hg with intravenous nicardipine; 11C-PIB-PET imaging and magnetic resonance imaging (MRI) were also obtained. There were no significant differences in mean CBF before and after MAP reduction in the bilateral hemispheres (−0.9±5.2 mL per 100 g per minute, P=0.4, 95% confidence interval (CI)=−3.4 to 1.5), cortical borderzones (−1.9±5.0 mL per 100 g per minute, P=0.10, 95% CI=−4.3 to 0.4), regions of T2W-MRI-defined leukoaraiosis (−0.3±4.4 mL per 100 g per minute, P=0.85, 95% CI=−3.3 to 3.9), or regions of peak 11C-PIB uptake (−2.5±7.7 mL per 100 g per minute, P=0.30, 95% CI=−7.7 to 2.7). The absence of significant change in CBF with a 10 to 15 mm Hg reduction in MAP within the normal autoregulatory range demonstrates that there is neither a generalized nor local defect of autoregulation in AD.


2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Li Zuo ◽  
Benjamin T. Hemmelgarn ◽  
Chia-Chen Chuang ◽  
Thomas M. Best

An increasing number of studies have proposed a strong correlation between reactive oxygen species (ROS)-induced oxidative stress (OS) and the pathogenesis of Alzheimer’s disease (AD). With over five million people diagnosed in the United States alone, AD is the most common type of dementia worldwide. AD includes progressive neurodegeneration, followed by memory loss and reduced cognitive ability. Characterized by the formation of amyloid-beta (Aβ) plaques as a hallmark, the connection between ROS and AD is compelling. Analyzing the ROS response of essential proteins in the amyloidogenic pathway, such as amyloid-beta precursor protein (APP) and beta-secretase (BACE1), along with influential signaling programs of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and c-Jun N-terminal kinase (JNK), has helped visualize the path between OS and Aβoverproduction. In this review, attention will be paid to significant advances in the area of OS, epigenetics, and their influence on Aβplaque assembly. Additionally, we aim to discuss available treatment options for AD that include antioxidant supplements, Asian traditional medicines, metal-protein-attenuating compounds, and histone modifying inhibitors.


1998 ◽  
Vol 10 (2) ◽  
pp. 193-203 ◽  
Author(s):  
John O. Brooks ◽  
Jerome A. Yesavage ◽  
Angelico Carta ◽  
Daniele Bravi

Objectives: To assess the longitudinal effects of acetyl-L-carnitine (ALC) on patients diagnosed with Alzheimer's disease. Design: Longitudinal, double-blind, parallel-group, placebocontrolled. Setting: Twenty-four outpatient sites across the United States. Participants: A total of 334 subjects diagnosed with probable Alzheimer's disease by NINCDS-ADRDA criteria. These data were originally reported by Thal and colleagues (1996). Measurements: Cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS) given every 3 months for 1 year. Results: The average rate of change was estimated using the trilinear approach, which allows for periods of both change and stability. Both the ALC group and the placebo group exhibited the same mean rate of change on the ADAS (0.68 points/month). However, a multiple regression analysis revealed a statistically significant Age × Drug interaction characterized by younger subjects benefiting more from ALC treatment than older subjects. Further analyses suggested that the optimal, though not statistically significant, cutpoint for ALC benefit was 61 years of age. Conclusions: ALC slows the progression of Alzheimer's disease in younger subjects, and the use of the trilinear approach to estimate the average rate of change may prove valuable in pharmacological trials.


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