Beta Amyloid Peptide: Research Paper : Assessing the Impact of Factors that Influence the Ketogenic Response to Varying Doses of Medium Chain Triglyceride (MCT) Oil

Assessing the Impact of Factors that Influence the Ketogenic Response to Varying Doses of Medium Chain Triglyceride (MCT) Oil

Abstract

Objectives, Design, Setting: The ketogenic effect of medium chain triglyceride (MCT) oil offers potential for Alzheimer's disease prevention and treatment. Limited literature suggests a linear B-hyroxybutyrate (BHB) response to increasing MCT doses. This pharmacokinetic study evaluates factors affecting BHB response in three subject groups.

Participants: Healthy subjects without cognitive deficits <65years, similarly healthy subjects >=65years, and those with Alzheimer's Disease were assessed.

Intervention: Different doses (0g,14g, 28g, 42g) of MCT oil (99.3% C8:0) were administered, followed by fasting during the study period.

Measurements: BHB measured by finger prick sampling hourly for 5 hours after ingestion. Each subject attended four different days for each ascending dose. Data was also collected on body composition, BMI, waist/hip ratio, grip strength, gait speed, nutrient content of pre-study breakfast and side effects.

Results: Twenty-five participants: eight healthy; average age of 44yr (25-61), nine healthy; 79yr (65-90) and eight with AD; 78.6yr (57-86) respectively. Compiled data showed the expected linear dose response relationship. No group differences, with baseline corrected area under the blood vs. time curve (r2=0.98) and maximum concentrations (r2=0.97). However, there was notable individual variability in maximum BHB response (42g dose: 0.4 -2.1mM), and time to reach maximum BHB response both, within and between individuals. Variability was unrelated to age, sex, sarcopenic or AD status. Visceral fat, BMI, waist/hip ratio and pretest meal CHO and protein content all affected the BHB response (p<0.001).

Conclusion: There was a large inter-individual variability, with phenotype effects identified. This highlights challenges in interpreting clinical responses to MCT intake.

Keywords: Alzheimer's disease; B-hydroxybutyrate; body composition; coconut oil; medium chain triglyceride (MCT); pharmacokinetic.

Conflict of interest statement

Angela G Juby, Dion R Brocks, David A Jay, Christopher MJ Davis, Diana R Mager, all have no conflicts of interest with respect to this study.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33336220/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: Research Paper : Polygenic Risk Scoring is an Effective Approach to Predict Those Individuals Most Likely to Decline Cognitively Due to Alzheimer's Disease

Polygenic Risk Scoring is an Effective Approach to Predict Those Individuals Most Likely to Decline Cognitively Due to Alzheimer's Disease

Abstract

Background: There is a clear need for simple and effective tests to identify individuals who are most likely to develop Alzheimer's Disease (AD) both for the purposes of clinical trial recruitment but also for improved management of patients who may be experiencing early pre-clinical symptoms or who have clinical concerns.

Objectives: To predict individuals at greatest risk of progression of cognitive impairment due to Alzheimer's Disease in individuals from the Alzheimer's Disease Neuroimaging Initiative (ADNI) using a polygenic risk scoring algorithm. To compare the performance of a PRS algorithm in predicting cognitive decline against that of using the pTau/Aß1-42 ratio CSF biomarker profile.

Design: A longitudinal analysis of data from the Alzheimer's Disease Neuroimaging Initiative study conducted across over 50 sites in the US and Canada.

Setting: Multi-center genetics study.

Particpants: 515 subjects who upon entry to the study were diagnosed as cognitively normal or with mild cognitive impairment.

Measurements: Use of genotyping and/or whole genome sequencing data to calculate polygenic risk scores and assess ability to predict subsequent cognitive decline as measured by CDR-SB and ADAS-Cog13 over 4 years.

Results: The overall performance for predicting those individuals who would decline by at least 15 ADAS-Cog13 points from a baseline mild cognitive impairment in 4 years was 72.8% (CI:67.9-77.7) AUC increasing to 79.1% (CI: 75.6-82.6) when also including cognitively normal participants. Assessing mild cognitive impaired subjects only and using a threshold of greater than 0.6, the high genetic risk participant group declined, on average, by 1.4 points (CDR-SB) more than the low risk group over 4 years. The performance of the PRS algorithm tested was similar to that of the pTau/Aß1-42 ratio CSF biomarker profile in predicting cognitive decline.

Conclusion: Calculating polygenic risk scores offers a simple and effective way, using DNA extracted from a simple mouth swab, to select mild cognitively impaired patients who are most likely to decline cognitively over the next four years.

Keywords: Alzheimer's disease; Polygenic risk; cognitive decline.

Conflict of interest statement

P. Daunt, A.Gibson, O.Oshota and R. Pither are all employees of Cytox Ltd. G. Davidson received payment from Cytox Ltd. for work done both within and outside the scope of this article.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33336228/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: Research Paper : Is Reluctance to Share Alzheimer's Disease Biomarker Status with a Study Partner a Barrier to Preclinical Trial Recruitment?

Is Reluctance to Share Alzheimer's Disease Biomarker Status with a Study Partner a Barrier to Preclinical Trial Recruitment?

Abstract

Background: Preclinical Alzheimer's disease clinical trials test candidate treatments in individuals with biomarker evidence but no cognitive impairment. Participants are required to co-enroll with a knowledgeable study partner, to whom biomarker information is disclosed.

Objective: We investigated whether reluctance to share biomarker results is associated with viewing the study partner requirement as a barrier to preclinical trial enrollment.

Design: We developed a nine-item assessment on views toward the study partner requirement and performed in-person interviews based on a hypothetical clinical trial requiring biomarker testing and disclosure.

Setting: We conducted interviews on campus at the University of California, Irvine.

Participants: Two hundred cognitively unimpaired older adults recruited from the University of California, Irvine Consent-to-Contact Registry participated in the study.

Measurements: We used logistic regression models, adjusting for potential confounders, to examine potential associations with viewing the study partner requirement as a barrier to preclinical trial enrollment.

Results: Eighteen percent of participants reported strong agreement that the study partner requirement was a barrier to enrollment. Ten participants (5%) agreed at any level that they would be reluctant to share their biomarker result with a study partner. The estimated odds of viewing the study partner requirement as a barrier to enrollment were 26 times higher for these participants (OR=26.3, 95% CI 4.0, 172.3), compared to those who strongly disagreed that they would be reluctant to share their biomarker result. Overall, participants more frequently agreed with positive statements than negative statements about the study partner requirement, including 76% indicating they would want their study partner with them when they learned biomarker results.

Conclusions: This is one of the first studies to explore how potential preclinical Alzheimer's disease trial participants feel about sharing their personal biomarker information with a study partner. Most participants viewed the study partner as an asset to trial enrollment, including having a partner present during biomarker disclosure.

Keywords: Alzheimer's disease; biomarker; disclosure.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33336225/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: Research Paper : Nutrition to Prevent or Treat Cognitive Impairment in Older Adults: A GRADE Recommendation

Nutrition to Prevent or Treat Cognitive Impairment in Older Adults: A GRADE Recommendation

Abstract

Aging is associated with cognitive declines leading to mild cognitive impairments or Alzheimer disease. Nutrition appear to protect from aging. Some dietary factors could either increase or protect against cognitive declines. This article aimed to provide GRADE recommendations related to nutrition aspects able to prevent or to treat cognitive impairments. A comprehensive literature review was performed using Medline database. The GRADE approach was used to classify quality of the existing evidence (systematic review or meta-analysis).The GRADE process led us to formulate seven key nutritional recommendations to manage cognitive declines, but did not allow us to do it for protein, vitamin B or antioxidants. Thus, 1) adherence to a Mediterranean diet (GRADE 1B); 2) high-level of consumption of mono- or poly- unsaturated fatty acids combined to a low consumption of saturated fatty acids (GRADE 1B); 3) high consumption of fruits and vegetables (GRADE 1B); 4) higher vitamin D intake (GRADE 1C) than the recommended daily allowance. In addition, a ketogenic diet, a low consumption of whole-fat dairy products or a caloric restriction are promising nutritional habits although the evidence does not yet support widespread uptake (GRADE 2C). In conclusion, nutrition is an important modifiable factor to prevent or protect against cognitive decline. Nevertheless, more studies are required to determine specific guidelines such as duration and amounts of nutrients to help older adult to maintain a healthy cognitive life.

Keywords: GRADE process; aging; cognitive impairment; diet guidelines.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33336232/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: Research Paper : A Systematic Review on the Feasibility of Salivary Biomarkers for Alzheimer's Disease

A Systematic Review on the Feasibility of Salivary Biomarkers for Alzheimer's Disease

Abstract

Early AD diagnosis is critical for ameliorating prognosis and treatment. The analysis of CSF biomarkers yields accurate results, but it necessitates a lumbar puncture procedure. Screening for peripheral biomarkers in saliva is advantageous since this medium is noninvasive and inexpensive to obtain. The objective of this systematic review is to analyze saliva biomarker studies which aim to diagnose AD. Titles, abstracts, and reference lists for publications from January 2004 to February 2020 were screened for by searching Google Scholar and PubMed. The inclusion criteria involved published studies that consisted of both AD and control groups. 88 studies were screened, and 20 publications fulfilled the inclusion criteria. These selected publications were scrutinized and included in this review. Aβ42, tau, certain metabolites, and oral microbiota might serve as reliable biomarkers for AD diagnosis. These results showcase the legitimate feasibility of proteomic, metabolomic, and microbiotic compounds in saliva for AD diagnostics in the near future. Supplemental studies must consider standardizing the analytical methods of measuring salivary biomarkers to establish coherence for the selection of valid AD biomarkers. Validation studies will require a large sample size of biomarker-diagnosed individuals for independent populations. This ensures accuracy and rigidity for receiver operating characteristic (ROC) curves that can be set for the most optimal salivary biomarkers in future clinical settings.

Keywords: Alzheimer; biomarker; dementia; saliva.

Conflict of interest statement

The author declares no potential conflicts of interest.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33336229/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: Research Paper : Ongoing Research Protocols for the Pharmacological Treatment of Neuropsychiatric Symptoms in Dementia

Ongoing Research Protocols for the Pharmacological Treatment of Neuropsychiatric Symptoms in Dementia

Abstract

The implementation of effective interventions for neuropsychiatric symptoms (NPS) is perceived as one of the most pressing research priorities in the field of dementia and one of the main unmet needs from the perspective of affected individuals and their caregivers and relatives. Nevertheless, to date, only a relatively marginal part of dementia research has focused on NPS. This study aimed to describe and discuss the state of the art concerning the identification and development of new pharmacological treatments for NPS in dementia. A review of 320 ongoing phase 1, 2, 3, and 4 protocols registered in the clinicaltrials.gov database was performed. All the trials enrolling patients with dementia were selected. Only studies adopting clinical measures of NPS frequency and/or severity as primary outcome were retained and analyzed. Overall, only a minority of ongoing phase 1, 2, 3 and 4 protocols on dementia (i.e., 9.0%) is primarily targeting NPS. Most of these studies are adopting a placebo-controlled parallel assignment design, testing oral compounds, and targeting specific NPS (mostly agitation and/or aggression). A total of 3,445 subjects with dementia will tentatively be recruited in these trials. The methodologies adopted in these studies, the characteristics of the tested interventions, the eligibility criteria, and the operational definitions of NPS are presented and discussed. The relevance of NPS is not yet matched by an adequate research effort. The current tendency at privileging disease-modifying approaches and other symptoms of dementia and the methodological complexity of studying NPS are still substantially contributing to the gap between research activities and clinical needs.

Keywords: Dementia; behavioral and psychological symptoms of dementia; neuropsychiatric symptoms.

Conflict of interest statement

Authors have no competing interest to disclose for the present study. Marco Canevelli is supported by a research grant of the Italian Ministry of Health (GR-2016-02364975) for the project "Dementia in immigrants and ethnic minorities living in Italy: clinical-epidemiological aspects and public health perspectives" (ImmiDem). Matteo Cesari has received honoraria for presentations at scientific meetings and/or research funding from Nestlé and Pfizer. He is involved in the coordination of an Innovative Medicines Initiative-funded project (including partners from the European Federation Pharmaceutical Industries and Associates [Sanofi, Novartis, Servier, GSK, Lilly]).

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33331618/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: Research Paper : The association between toxic pesticide environmental exposure and Alzheimer's disease: A scientometric and visualization analysis

The association between toxic pesticide environmental exposure and Alzheimer's disease: A scientometric and visualization analysis

Abstract

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases. The association between environmental factors (e.g., pesticide) and AD has attracted considerable attention. However, no systematic analysis has been performed and make it difficult to provide deeper insights of AD correlated with pesticide exposure. Hence, this study utilized a bibliometric and visual approach that included map collaborations, co-citations, and keywords, to identifying the knowledge structure, hot topics and the research trends based on 372 publications from the Web of Science Core Collection and PubMed databases. The results showed that 116 institutions from 52 countries published articles in this field. The United States and Israel played a leading role with numerous publications in related journals, as well as prolific institutions and authors, respectively. Three hot topics in pesticide-induced AD were recognized based on co-occurrence keywords detection, including acetylcholinesterase (AChE) inhibitor, oxidative stress, and AChE. Moreover, analysis of keywords burst suggests that some potential molecular mechanisms and therapy targets of pesticide-induced AD, especially for mitochondrial dysfunction and monoamine oxidase-B (MAO-B) that catalyzes the oxidative deamination and causes oxidative stress, are emerging trends. In addition, the study of various pesticides and the assessment method of pesticide exposure will step forward as well. To the best of our knowledge, this study is the first to specifically visualize the relationship between AD and pesticide exposure and to predict potential future research directions.

Keywords: Alzheimer's disease; Bibliometric analysis; Citespace; Environmental toxins; Knowledge mapping; Pesticides.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33297185/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: Research Paper : Decreased Proteasomal Function Induces Neuronal Loss and Memory Impairment

Decreased Proteasomal Function Induces Neuronal Loss and Memory Impairment

Abstract

Alzheimer disease (AD) is a progressive neurodegenerative disorder and the most common type of dementia worldwide. There is considerable evidence of age-related disruption of proteostasis being responsible for the development of AD. The proteasome is a multicatalytic enzyme complex that degrades both normal and damaged proteins, and an age-related decline in its activity has been implicated in age-related pathologies. Although proteasomal dysfunction is assumed to be a key AD hallmark, it remains unclear whether its role in disease onset is causative or secondary. In this study, we demonstrate that mice with proteasomal dysfunction exhibited memory impairment with associated neuronal loss, accumulation of phosphorylated tau, and activation of endoplasmic reticulum (ER) stress-related apoptosis pathways. Impaired proteasomal activity also activated ER stress-related apoptosis pathways in HT-22, a murine hippocampal neuronal cell line. HT-22 cell death, caused by proteasomal inhibition, was prevented by an inhibitor of c-Jun N-terminal kinase, an ER stress-related molecule. Collective evidence suggests that impaired proteasomal activity alters proteostasis, and subsequent ER stress-mediated pathways play pivotal roles in neuronal loss. Because aging decreases proteasomal function, age-related impairment of proteasomes may be involved in the development and progression of AD in elderly patients.

Copyright © 2021 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33339546/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: Research Paper :

Resveratrol: A "miracle" drug in neuropsychiatry or a cognitive enhancer for mice only? A systematic review and meta-analysis

Abstract

Background: Over the last decade resveratrol has been trialled for the prevention and treatment of cognitive decline; however, the results have shown a conflict between human studies compared with animal studies, especially on cognition, blood pressure, neuroimaging, and mood.

Methods: Human clinical trials and animal studies published prior to January 2020, were identified searching across major electronic databases. PRISMA guidelines were used for data extraction, which was independently performed by two authors. Pooled standard mean difference (SMD, random effect model) and odds ratios (ORs) were calculated.

Results: Most publications on animal models reported positive outcomes on cognition and brain function following exposure to resveratrol or grape seed extracts. By contrast, 11 meta-analyses of data from human placebo vs resveratrol, grape or wine treatment trials identified no statistically significant effect on a variety of measures, including cognitive and mood assessments, grey matter volume and blood pressure.

Conclusions: Based on currently available data, the promising effects of resveratrol in animal models is not replicated in human clinical trials. The effects, if any, of resveratrol on human cognition are likely to be small. This work may be useful for the design and implementation of future pre-clinical and clinical studies using resveratrol in a neurological setting.

Keywords: Alzheimer's; Cognition; Dementia; Meta-analysis; Natural products; Resveratrol; Systematic review.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33303422/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: Research Paper : Recent Advances in the Potential of Cannabinoids for Neuroprotection in Alzheimer's, Parkinson's, and Huntington's Diseases

Recent Advances in the Potential of Cannabinoids for Neuroprotection in Alzheimer's, Parkinson's, and Huntington's Diseases

Abstract

Three prevalent neurodegenerative diseases, Parkinson's, Alzheimer's, and Huntington's are in need of symptomatic relief of slowing disease progression or both. This chapter focuses on the potential of cannabinoids to afford neuroprotection, i.e. avoid or retard neuronal death. The neuroprotective potential of cannabinoids is known from the work in animal models and is mediated by the two cannabinoid receptors (CB1/CB2) and eventually, by their heteromers, GPR55, orphan receptors (GPR3/GPR6/GPR12/GPR18), or PPARγ. Now, there is the time to translate the findings into patients. The chapter takes primarily into account advances since 2016 and addresses the issue of proving neuroprotection in humans. One recent discovery is the existence of activated microglia with neuroprotective phenotype; cannabinoids are good candidates to skew phenotype, especially via glial CB2 receptors (CB2R), whose targeting has, a priori, less side effects those targeting the CBs1 receptor (CB1R), which are expressed in both neurons and glia. The fact that a cannabis extract (SativexTM) is approved for human therapy, such that cannabis use will likely be legalized in many countries and different possibilities that cannabinoid pharmacology suggests a successful route of cannabinoids (natural or synthetic) all the way to be approved and used in the treatment of neurodegeneration.

Keywords: Dementia; Drug discovery; Fatty acid amide hydrolase; Heteromers; Microglia; Neurodegenerative diseases; Nootropics; Therapy.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33332005/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: Research Paper : Effects of Glutamate Arginylation on α-Synuclein: Studying an Unusual Post-Translational Modification through Semisynthesis

Effects of Glutamate Arginylation on α-Synuclein: Studying an Unusual Post-Translational Modification through Semisynthesis

Abstract

A variety of post-translational modifications (PTMs) are believed to regulate the behavior and function of α-synuclein (αS), an intrinsically disordered protein that mediates synaptic vesicle trafficking. Fibrils of αS are implicated in neurodegenerative disorders such as Parkinson's disease. In this study, we used chemical synthesis and biophysical techniques to characterize the neuroprotective effects of glutamate arginylation, a hitherto little characterized PTM in αS. We developed semisynthetic routes combining peptide synthesis, unnatural amino acid mutagenesis, and native chemical ligation (NCL) to site-specifically introduce the PTM of interest along with fluorescent probes into αS. We synthesized the arginylated glutamate as a protected amino acid, as well as a novel ligation handle for NCL, in order to generate full-length αS modified at various individual sites or a combination of sites. We assayed the lipid-vesicle binding affinities of arginylated αS using fluorescence correlation spectroscopy (FCS) and found that arginylated αS has the same vesicle affinity compared to control protein, suggesting that this PTM does not alter the native function of αS. On the other hand, we studied the aggregation kinetics of modified αS and found that arginylation at E83, but not E46, slows aggregation and decreases the percentage incorporation of monomer into fibrils in a dose-dependent manner. Arginylation at both sites also resulted in deceleration of fibril formation. Our study represents the first synthetic strategy for incorporating glutamate arginylation into proteins and provides insight into the neuroprotective effect of this unusual PTM.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33337869/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.