Emma Shardlow, Bakhtbilland Khan, Christopher Exley
BACKGROUND AND AIM: Aβ1-42 is an amyloidogenic peptide found within senile plaques extracted from those who died with a diagnosis of Alzheimer's disease. The potent neurotoxicity of this peptide is related to its propensity to form aggregated conformations in vivo, a process that is influenced by the species and concentration of metal ions present within the local environment. This study examines the impact of different metals upon the early aggregatory behaviour and size of Aβ1-42 under simulated physiological conditions...
May 3, 2021: Journal of Trace Elements in Medicine and Biology
Sheida Rabipour, Sricharana Rajagopal, Stamatoula Pasvanis, M Natasha Rajah
Late-onset Alzheimer's disease (AD) disproportionately affects women compared to men. Episodic memory decline is one of the earliest and most pronounced deficits observed in AD. However, it remains unclear whether sex influences episodic memory-related brain function in cognitively intact older adults at risk of developing AD. Here we used task-based multivariate partial least squares analysis to examine sex differences in episodic memory-related brain activity and brain activity-behavior correlations in a matched sample of cognitively intact older women and men with a family history of AD from the PREVENT-AD cohort study in Montreal, Canada (Mage =63...
April 1, 2021: Neurobiology of Aging
John Saathoff, Jakob Green, Yuqi Jiang, Yiming Xu, Glen E Kellogg, Shijun Zhang
In our continuing efforts to develop novel neuroprotectants for Alzheimer's disease (AD), a series of analogs based on a lead compound that was recently shown to target the mitochondrial complex I were designed, synthesized and biologically characterized to understand the structure features that are important for neuroprotective activities. The results from a cellular AD model highlighted the important roles of the 4-OH on the phenyl ring and the 5-OCH3 on the indole ring of the lead compound. The results also demonstrated that the β-keto moiety can be modified to retain or improve the neuroprotective activity...
May 5, 2021: Bioorganic & Medicinal Chemistry Letters
Yi Huang, Weiwei Huang, Guixiang Yang, Rui Wang, Lei Ma
Alzheimer's disease is a progressive neurodegenerative disease, and its incidence is expected to increase as the global population ages. Recent studies provide increasing evidence that inflammation plays a key role in the pathogenesis and progression of AD. Diosgenin, an active ingredient in Dioscorea nipponica Makino, is a promising bioactive lead compound in the treatment of Alzheimer's disease, which exhibited anti-inflammatory activity. To search for more efficient anti-Alzheimer agents, a series of novel diosgenin-triazolyl hybrids were designed, synthesized, and their neuroprotective effects against oxygen-glucose deprivation-induced neurotoxicity and LPS-induced NO production were evaluated...
May 5, 2021: Bioorganic & Medicinal Chemistry Letters
Keyin Shen, Xingran Liu, Dandan Chen, Jingru Chang, Ying Zhang, Xianjuan Kou
Autophagy is a highly regulated intracellular process for the degradation of protein aggregates and damaged organelles. Recently, autophagy has been implicated in Alzheimer's disease (AD) and aging. Autophagy process is regulated by the recruitment and assembly of several autophagy-related genes (Atgs) such as, Atg7 and LC3, as the highly conserved and important markers involved in the regulation of autophagy. We recently reported the reduced LC3-II/LC3-I ratio, down-regulated ATG7, and increased p62 protein levels in hippocampal tissues of aging rats...
May 5, 2021: Brain Research Bulletin
Yves Rolland, Celine Mathieu, Neda Tavassoli, Emilie Berard, Clarisse Laffon de Mazières, Sophie Hermabessière, Mathieu Houles, Amélie Perrin, Thomas Krams, Soraya Qassemi, Amandine Cambon, Elodie Magre, Christelle Cantet, Sandrine Charpentier, Dominique Lauque, Olivier Azema, Bruno Chicoulaa, Stéphane Oustric, Cécile McCambridge, Eugénie Gombault-Datzenko, Laurent Molinier, Nadège Costa, Philipe De Souto Barreto
OBJECTIVES: To determine the factors associated with the potentially inappropriate transfer of nursing home (NH) residents to emergency departments (EDs) and to compare hospitalization costs before and after transfer of individuals addressed inappropriately vs those addressed appropriately. DESIGN: Multicenter, observational, case-control study. SETTING AND PARTICIPANTS: 17 hospitals in France, 1037 NH residents. MEASURES: All NH residents transferred to the 17 public hospitals' EDs in southern France were systematically included for 1 week per season...
May 5, 2021: Journal of the American Medical Directors Association
Emilie W Kjeldsen, Jesper Q Thomassen, Ida Juul Rasmussen, Børge G Nordestgaard, Anne Tybjærg-Hansen, Ruth Frikke-Schmidt
AIMS: The association of plasma high-density lipoprotein (HDL) cholesterol with risk of dementia is unclear. We therefore tested the hypothesis that high levels of plasma HDL cholesterol are associated with increased risk of dementia and whether a potential association is of a causal nature. METHODS AND RESULTS: In two prospective population-based studies, the Copenhagen General Population Study and the Copenhagen City Heart Study (N = 111,984 individuals), we first tested whether high plasma HDL cholesterol is associated with increased risk of any dementia and its subtypes...
May 8, 2021: Cardiovascular Research
Shuhua Shen, Xiaoming Wang, Hang Lv, Yuan Shi, Luwei Xiao
The effects of PADI4 and GAA on the senescence of Alzheimer's cells were explored in the present work. HT22 cells were treated with Aβ25-35 to establish an Alzheimer's model, and were then treated with different concentrations of GAA and transfected with a siPADI4 lentiviral vector. GAA could reverse the effects of Aβ25-35 on inhibiting cell viability and promoting apoptosis and senescence. siPADI4 reduced Aβ25-35 induced cell viability and up-regulated Aβ25-35 induced cell apoptosis and senescence, as well as partially reversed the effect of GAA on cells, and these results were confirmed by detecting the expressions of senescence- and apoptosis-related proteins...
May 8, 2021: Bioscience, Biotechnology, and Biochemistry
Pei-Liang Dong, ZhengQing Li, Cui-Li Teng, Xin Yin, Xian-Kai Cao, Hua Han
While screening for natural product scaffolds as potential anti Alzheimer's disease (AD), oxymatrine (OMT) was found to relieve symptoms of AD through diminishing death of neuronal cells caused by microglia induced inflammation. In this study, 13 derivatives of OMT were synthesized and their neuroprotective effects were evaluated on Aβ1-42 induced PC12 cells using MTT method. In addition, the best neuroprotective potencies were obtained with compounds 4, 6e and 6f, which were selected for evaluation of decrease of IL-1β and TNF-α in Aβ1-42 -treated PC12 cells...
May 7, 2021: Chemical Biology & Drug Design
Joni Marcio de Farias, Natalia Dos Santos Tramontin, Eduarda Valim Pereira, Geiziane Laurindo de Moraes, Beatriz Giusti Furtado, Lariani Tamires Witt Tietbohl, Bárbara Da Costa Pereira, Kellen Ugioni Simon, Alexandre Pastoris Muller
Alzheimer's disease (AD) is characterized by progressive impairment of memory, with an etiology involving oxidative stress and inflammation. Exercise training is a safe, efficacious, and economic approach to manage neurodegenerative diseases. In AD, the biomarkers of oxidative damage to lipids, proteins, and DNA are elevated. In the present study, we aimed to evaluate whether exercise is effective in patients with AD by assessing the serum biomarkers associated with the redox status, neurotrophin levels, and inflammatory system...
May 7, 2021: Molecular Neurobiology
Deborah A Levine, Andrzej T Galecki, Brenda L Plassman, Angela Fagerlin, Lauren P Wallner, Kenneth M Langa, Rachael T Whitney, Brahmajee K Nallamothu, Lewis B Morgenstern, Bailey K Reale, Emilie M Blair, Bruno Giordani, Kathleen Anne Welsh-Bohmer, Mohammed U Kabeto, Darin B Zahuranec
BACKGROUND: Older patients (65+) with mild cognitive impairment (MCI) receive less guideline-concordant care for cardiovascular disease (CVD) and other conditions than patients with normal cognition (NC). One potential explanation is that patients with MCI want less treatment than patients with NC; however, the treatment preferences of patients with MCI have not been studied. OBJECTIVE: To determine whether patients with MCI have different treatment preferences than patients with NC...
May 7, 2021: Journal of General Internal Medicine
David W Radke, Jae Hoon Sul, Daniel J Balick, Sebastian Akle, Robert C Green, Shamil R Sunyaev
Genomic deletions provide a powerful loss-of-function model in noncoding regions to assess the role of purifying selection on genetic variation. Regulatory element function is characterized by nonuniform tissue and cell type activity, necessarily linking the study of fitness consequences from regulatory variants to their corresponding cellular activity. We generated a callset of deletions from genomes in the Alzheimer's Disease Neuroimaging Initiative (ADNI) and used deletions from The 1000 Genomes Project Consortium (1000GP) in order to examine whether purifying selection preserves noncoding sites of chromatin accessibility marked by DNase I hypersensitivity (DHS), histone modification (enhancer, transcribed, Polycomb-repressed, heterochromatin), and chromatin loop anchors...
May 7, 2021: Genome Research
Louise Dunphy, Tosin Akin-Komolafe, Zac Etheridge
It is well recognised that acute confusion or delirium complicates up to 10% of acute medical admissions. Disorientation in time and place with an impaired short-term memory and conscious level are the hallmarks of an acute confusion. In delirium, disorders of perception may produce restlessness and agitation. A similar state during the final days of life is termed 'terminal delirium'. Less than 10% of affected individuals will have a primary neurological disorder, for example, dementia, a neurodegenerative disease with varying aetiologies...
May 7, 2021: BMJ Case Reports
Manfred Berres, Andreas U Monsch, René Spiegel
BACKGROUND: The Placebo Group Simulation Approach (PGSA) aims at partially replacing randomized placebo-controlled trials (RPCTs), making use of data from historical control groups in order to decrease the needed number of study participants exposed to lengthy placebo treatment. PGSA algorithms to create virtual control groups were originally derived from mild cognitive impairment (MCI) data of the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. To produce more generalizable algorithms, we aimed to compile five different MCI databases in a heuristic manner to create a "standard control algorithm" for use in future clinical trials...
May 7, 2021: Alzheimer's Research & Therapy
Abhishek Ankur Balmik, Subashchandrabose Chinnathambi
Neurodegenerative diseases like Alzheimer's, Parkinson's and Huntington's disease involves abnormal aggregation and accumulation of toxic proteins aggregates. Post-translational modifications (PTMs) of the causative proteins play an important role in the etiology of disease as they could either slow down or accelerate the disease progression. Alzheimer disease is associated with the aggregation and accumulation of two major protein aggregates-intracellular neurofibrillary tangles made up of microtubule-associated protein Tau and extracellular Amyloid-β plaques...
May 7, 2021: Cell Communication and Signaling: CCS
Nur Syafiqah Rahim, Siong Meng Lim, Vasudevan Mani, Nurul Aqmar Mohamad Nor Hazalin, Abu Bakar Abdul Majeed, Kalavathy Ramasamy
Neuroinflammation is associated with neuronal cell death and could lead to chronic neurodegeneration. This study investigated the neuroprotective potential of virgin coconut oil (VCO) against lipopolysaccharide (LPS)-induced cytotoxicity of neuroblastoma SK-N-SH cells. The findings were validated using Wistar rats, which were fed with 1-10 g/kg VCO for 31 days, exposed to LPS (0.25 mg/kg) and subjected to the Morris Water Maze Test. Brain homogenate was subjected to biochemical analyses and gene expression studies...
October 14, 2020: Journal of Dietary Supplements
Gonzalo Sánchez-Benavides, Marc Suárez-Calvet, Marta Milà-Alomà, Eider M Arenaza-Urquijo, Oriol Grau-Rivera, Grégory Operto, Juan Domingo Gispert, Natalia Vilor-Tejedor, Aleix Sala-Vila, Marta Crous-Bou, José Maria González-de-Echávarri, Carolina Minguillon, Karine Fauria, Maryline Simon, Gwendlyn Kollmorgen, Henrik Zetterberg, Kaj Blennow, José Luis Molinuevo
Neurofilament light chain (NfL) is an axonal protein that when measured in cerebrospinal fluid (CSF) serves as a biomarker of neurodegeneration. We aimed at investigating the association among CSF NfL, presence of Subjective Cognitive Decline (SCD) and hippocampal volume, and how CSF amyloid-β (Aβ) modifies these associations. We included 278 cognitively unimpaired participants from the Alfa+ cohort (78 SCD and 200 Controls). Linear models accounting for covariates (age, gender, and mood) were used to test the association between CSF NfL and SCD status, and between CSF NfL and bilateral hippocampal volumes...
March 6, 2021: Neurobiology of Aging
Paula Duarte-Guterman, Arianne Y Albert, Cindy K Barha, Liisa A M Galea, On Behalf Of The Alzheimer's Disease Neuroimaging Initiative
Alzheimer's disease (AD) is characterized by severe cognitive decline and pathological changes in the brain (brain atrophy, hyperphosphorylation of tau, and deposition of amyloid-beta protein). Females have greater neuropathology (AD biomarkers and brain atrophy rates) and cognitive decline than males, however these effects can depend on diagnosis (amnestic mild cognitive impairment (aMCI) or AD) and APOE genotype (presence of ε4 alleles). Using the ADNI database (N = 630 females, N = 830 males), we analyzed the effect of sex, APOE genotype (non-carriers or carriers of APOEε4 alleles), and diagnosis (cognitively normal (CN), early aMCI (EMCI), late aMCI (LMCI), probable AD) on cognition (memory and executive function), hippocampal volume, and AD biomarkers (CSF levels of amyloid beta, tau, and ptau)...
April 29, 2021: Psychoneuroendocrinology
Jia Ke, Qinfang Tian, Qixia Xu, Zhenqin Fu, Qiang Fu
Alzheimer's disease (AD) is an irreversible neurodegenerative brain disorder which manifests as a progressive decline in cognitive function. Mitochondrial dysfunction plays a critical role in the early stages of AD, and increases the incidence {AuQ: Increases the incidence or advances the progression?} of this age-related neurodegenerative disorder. Therefore, it can be a potential target for interventions to treat AD. Several therapeutic strategies to target mitochondrial dysfunction have gained significant attention in the preclinical stage, but the clinical trials performed to date have shown little progress...
May 4, 2021: Drug Discovery Today
Natália Oiring de Castro Cezar, Ivan Aprahamian, Juliana Hotta Ansai, Marcos Paulo Braz de Oliveira, Danielle Chagas Pereira da Silva, Wildja de Lima Gomes, Bruna Anzolin Barreiros, Tamiris de Cássia Oliva Langelli, Larissa Pires de Andrade
OBJECTIVES: There is a need for interventions to reduce frailty in older people with Alzheimer's dementia (AD). The purpose of this study was to investigate the effect of a home-based multimodal exercise program for older adults with AD (AD-HOMEX) on frailty. DESIGN: A parallel single-blind randomized controlled trial comparing a home-based exercise program and usual care. SETTING AND PARTICIPANTS: A home-based program in Brazil. Forty individuals aged 65years or older with mild to moderate AD...
May 5, 2021: Experimental Gerontology
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