Satoshi Saito, Keisuke Suzuki, Ryo Ohtani, Takakuni Maki, Hisatomo Kowa, Hisatsugu Tachibana, Kazuo Washida, Nobuya Kawabata, Toshiki Mizuno, Rie Kanki, Shinji Sudoh, Hiroshi Kitaguchi, Katsuro Shindo, Akihiro Shindo, Nobuyuki Oka, Keiichi Yamamoto, Fumihiko Yasuno, Chikage Kakuta, Ryosuke Kakuta, Yumi Yamamoto, Yorito Hattori, Yukako Takahashi, Yuriko Nakaoku, Shuichi Tonomura, Naoya Oishi, Toshihiko Aso, Akihiko Taguchi, Tatsuo Kagimura, Shinsuke Kojima, Masanori Taketsuna, Hidekazu Tomimoto, Ryosuke Takahashi, Hidenao Fukuyama, Kazuyuki Nagatsuka, Haruko Yamamoto, Masanori Fukushima, Masafumi Ihara
IMPORTANCE: Recent evidence indicates the efficacy of β-amyloid immunotherapy for the treatment of Alzheimer disease, highlighting the need to promote β-amyloid removal from the brain. Cilostazol, a selective type 3 phosphodiesterase inhibitor, promotes such clearance by facilitating intramural periarterial drainage. OBJECTIVE: To determine the safety and efficacy of cilostazol in mild cognitive impairment. DESIGN, SETTING, AND PARTICIPANTS: The COMCID trial (A Trial of Cilostazol for Prevention of Conversion from Mild Cognitive Impairment to Dementia) was an investigator-initiated, double-blind, phase 2 randomized clinical trial...
December 1, 2023: JAMA Network Open
Niklas Mattsson-Carlgren, Lyduine E Collij, Erik Stomrud, Alexa Pichet Binette, Rik Ossenkoppele, Ruben Smith, Linda Karlsson, Juan Lantero-Rodriguez, Anniina Snellman, Olof Strandberg, Sebastian Palmqvist, Nicholas J Ashton, Kaj Blennow, Shorena Janelidze, Oskar Hansson
IMPORTANCE: Antiamyloid immunotherapies against Alzheimer disease (AD) are emerging. Scalable, cost-effective tools will be needed to identify amyloid β (Aβ)-positive patients without an advanced stage of tau pathology who are most likely to benefit from these therapies. Blood-based biomarkers might reduce the need to use cerebrospinal fluid (CSF) or positron emission tomography (PET) for this. OBJECTIVE: To evaluate plasma biomarkers for identifying Aβ positivity and stage of tau accumulation...
December 4, 2023: JAMA Neurology
Alan E Murphy, Nurun Fancy, Nathan Skene
Mathys et al. conducted the first single-nucleus RNA-seq (snRNA-seq) study of Alzheimer's disease (AD) (Mathys et al., 2019). With bulk RNA-seq, changes in gene expression across cell types can be lost, potentially masking the differentially expressed genes (DEGs) across different cell types. Through the use of single-cell techniques, the authors benefitted from increased resolution with the potential to uncover cell type-specific DEGs in AD for the first time. However, there were limitations in both their data processing and quality control and their differential expression analysis...
December 4, 2023: ELife
Mohd Shahnawaz Khan, Md Tabish Rehman, Gouse M Shaik, Abdulaziz Mohammed Alamri, Mohamed F AlAjmi, Mohammed Arshad, Majed S Alokail
Protein and peptide misfolding is a central factor in the formation of pathological aggregates and fibrils linked to disorders like Alzheimer's and Parkinson's diseases. Therefore, it's essential to understand how food additives, particularly Azorubine, affect protein structures and their ability to induce aggregation. In this study, human serum albumin (HSA) was used as a model protein to investigate the binding and conformational changes caused by azorubine, a common food and drink colorant. The research revealed that azorubine destabilized the conformation of HSA at both physiological (pH 7...
December 4, 2023: Journal of Biomolecular Structure & Dynamics
Martin Krátký, Karolína Nováčková, Katarína Svrčková, Markéta Švarcová, Šárka Štěpánková
Aim: 2-Thioxothiazolidin-4-one represents a versatile scaffold in drug development. The authors used it to prepare new potent acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors that can be utilized, e.g., to treat Alzheimer's disease. Materials & methods: 3-Amino-2-thioxothiazolidin-4-one was modified at the amino group or active methylene, using substituted benzaldehydes. The derivatives were evaluated for inhibition of AChE and BChE (Ellman's method). Results & conclusion: The derivatives were obtained with yields of 52-94%...
December 4, 2023: Future Medicinal Chemistry
Zachary Green, Paul Kueck, Casey John, Jeffrey Burns, Jill Morris
BACKGROUND: The development of biomarkers that are easy to collect, process, and store is a major goal of research on current Alzheimer's Disease (AD) and underlies the growing interest in plasma biomarkers. Biomarkers with these qualities will improve diagnosis and allow for better monitoring of therapeutic interventions. However, blood collection strategies have historically differed between studies. We examined the ability of various ultrasensitive plasma biomarkers to predict cerebral amyloid status in cognitively unimpaired individuals when collected using acid citrate dextrose (ACD)...
December 1, 2023: Current Alzheimer Research
Sian Jin, Xuefeng Guan, Dong-Yu Min
BACKGROUND: To evaluate the efficacy and pharmacological mechanisms of resveratrol in Alzheimer's disease (AD) patients. METHODS: We conducted a thorough exploration of existing randomized controlled trials concerning the treatment of Alzheimer's disease patients using resveratrol, utilizing accessible open databases. Quantitative variables were represented as a standardized mean difference (SMD), accompanied by a 95% confidence interval (CI). Additionally, we examined the potential targets and plausible pathways associated with the impact of resveratrol on Alzheimer's disease using network pharmacology techniques...
December 1, 2023: Current Alzheimer Research
Raymond L Ownby, Rosemary Davenport
OBJECTIVES: Evaluate the acceptability and efficacy of an online dementia prevention intervention based on a cognitive behavioral shared decision-making model. MATERIALS AND METHOD: This was an unblinded pilot study in which participants were randomly assigned to one of two treatment groups. SETTING: This study was carried out remotely via telephone, video conferencing, and online data collection. PARTICIPANTS: Eighteen English-speaking persons 40 years of age and older interested in developing more brain-healthy lifestyles...
December 1, 2023: Current Alzheimer Research
Bashayer A Khalifah, Shareefa A Alghamdi, Ali H Alhasan
Human transcriptome can undergo RNA mis-splicing due to spliceopathies contributing to the increasing number of genetic diseases including muscular dystrophy (MD), Alzheimer disease (AD), Huntington disease (HD), myelodysplastic syndromes (MDS). Intron retention (IR) is a major inducer of spliceopathies where two or more introns remain in the final mature mRNA and account for many intronic expansion diseases. Potential removal of such introns for therapeutic purposes can be feasible when utilizing bioinformatics, catalytic RNAs, and nano-drug delivery systems...
2023: Frontiers in Bioengineering and Biotechnology
Yu Lu, Piaopiao Zhang, Fenfen Xu, Yuan Zheng, Hongyang Zhao
Interleukin-17 (IL-17), a cytokine characteristically secreted by T helper 17 (Th17) cells, has attracted increasing attention in recent years because of its importance in the pathogenesis of many autoimmune or chronic inflammatory diseases. Recent studies have shown that neurological diseases and mental disorders are closely related to immune function, and varying degrees of immune dysregulation may disrupt normal expression of immune molecules at critical stages of neural development. Starting from relevant mechanisms affecting immune regulation, this article reviews the research progress of IL-17 in a selected group of neurological diseases and mental disorders (autism spectrum disorder, Alzheimer's disease, epilepsy, and depression) from the perspective of neuroinflammation and the microbiota-gut-brain axis, summarizes the commonalities, and provides a prospective outlook of target application in disease treatment...
2023: Frontiers in Neurology
Varalakshmi Kl, S R Anusha, Prajwal K Muthaiah, Harshini Jain Bs
Corpus callosum is one of the major association fibre of brain performs an integral role of integration and communication of information between the two hemispheres. 50 formalin fixed cerebral hemispheres (25 right and 25 left) were used for the study. The longitudinal and vertical length of brain, longitudinal length and height of corpus callosum, distance of corpus callosum from various landmarks such as frontal and occipital pole, anterior commissure, lamina terminalis, and highest point on parietal pole and width of different parts of corpus callosum and height were measured...
2023: Bioinformation
Bin Yang, Wenzheng Bao, Shichai Hong
[This corrects the article DOI: 10.3389/fnagi.2022.931729.].
2023: Frontiers in Aging Neuroscience
Dan Shi, Zikang Hao, Wenxiao Qi, Fengyi Jiang, Kerui Liu, Xiao Shi
Alzheimer's disease (AD) is a prevalent neurodegenerative disease account for 60-80% of the total number of people with dementia, but its treatment and prevention strategies are still in a long process of exploration. It has been reported that a healthy lifestyle may be an effective non-pharmacological intervention for the prevention and treatment of AD, including increased physical activity and the consumption of polyphenol-rich foods. This study, therefore, investigated the effects of 8 weeks of moderate-intensity aerobic exercise (EX), administration of chlorogenic acid administration (GCA), and a combination of both (EX+GCA) on β-amyloid (Aβ) deposition, inflammatory factors, oxidative stress markers, neuronal damage, and cognitive performance in the brains of AD model mice (APP/PS1) and which signaling pathways may be responsible for these effects...
2023: Frontiers in Aging Neuroscience
David J Libon, Emily Frances Matusz, Stephanie Cosentino, Catherine C Price, Rod Swenson, Meagan Vermeulen, Terrie Beth Ginsberg, Adaora Obiageli Okoli-Umeweni, Leonard Powell, Robert Nagele, Sean Tobyne, Joyce Rios Gomes-Osman, Alvaro Pascual-Leone
INTRODUCTION: Screening for neurocognitive impairment and psychological distress in ambulatory primary and specialty care medical settings is an increasing necessity. The Core Cognitive Evaluation™ (CCE) is administered/scored using an iPad, requires approximately 8 min, assesses 3- word free recall and clock drawing to command and copy, asks questions about lifestyle and health, and queries for psychological distress. This information is linked with patients' self- reported concerns about memory and their cardiovascular risks...
2023: Frontiers in Psychology
Huiyi Wu, Lei Huang, Shushan Zhang, Yang Zhang, Yajia Lan
OBJECTIVE: The complicated association of daytime napping, biological aging and cognitive function remains inconclusive. We aimed to evaluate the cross-sectional and longitudinal associations of daytime napping and two aging measures with cognition and to examine whether napping affects cognition through a more advanced state of aging. METHODS: Data was collected from the China Health and Retirement Longitudinal Study. Napping was self-reported. We calculated two published biological aging measures: Klemera and Doubal biological age (KDM-BA) and physiological dysregulation (PD), which derived information from clinical biomarkers...
2023: Frontiers in Public Health
Mariachiara Mengoli, Gabriele Conti, Marco Fabbrini, Marco Candela, Patrizia Brigidi, Silvia Turroni, Monica Barone
The microbiota-gut-brain axis refers to the intricate bidirectional communication between commensal microorganisms residing in the digestive tract and the central nervous system, along neuroendocrine, metabolic, immune, and inflammatory pathways. This axis has been suggested to play a role in several neurological disorders, such as Parkinson's disease, Alzheimer's disease, multiple sclerosis, and epilepsy, paving the way for microbiome-based intervention strategies for the mitigation and treatment of symptoms...
2023: Microbiome Res Rep
Shunya Morita, Zhaoyang Ren, Huafang Fan, Duy H Hua
Tricyclic pyrone (TP) molecules have shown protection of MC65 neuroblastoma cells death induced by amyloid-β proteins through SβC gene, a decrease of amyloid-β peptide levels, and improvement of motor functions and memory in Alzheimer's disease mouse and rat models. Mechanistic studies suggest TP molecules modulate N -methyl- D -aspartate receptor. A short synthesis of chiral TP analogs was sought using a Pd(0)-catalyzed displacement of TP allylic acetate intermediate with sodium azide or substituted benzylamines...
May 11, 2023: ChemistrySelect
Juhi Goyal, Preet Jain, Vivek Jain, Dibyajyoti Banerjee, Rajasri Bhattacharyya, Sharmistha Dey, Rambabu Sharma, Nitish Rai
Numerous studies have depicted the role of diet and environmental toxins in aging. Melamine (Mel) is a globally known notorious food adulterant, and its toxicity has been shown in several organs including the brain. However, till now, there are no reports regarding Mel neurotoxicity in aging neurons. So, this study examined the in vitro neurotoxicity caused by Mel in the D-galactose (DG)-induced aging model of neuronal SH-SY5Y cells. In the present study, the neuronal SH-SY5Y cells were treated with DG and Mel separately and in combination to assess the neurotoxicity potential using MTT assay and neurite length measurement...
2023: Journal of Aging Research
Sopak Supakul, Yuki Hatakeyama, Nicolas Leventoux, Maika Itsuno, Naoko Numata, Hayato Hiramine, Satoru Morimoto, Atsushi Iwata, Sumihiro Maeda, Hideyuki Okano
Human neural cell models derived from induced pluripotent stem cells (iPSCs) have been widely accepted to model various neurodegenerative diseases such as Alzheimer's disease (AD) in vitro . Although the most common sources of iPSCs are fibroblasts and peripheral blood mononuclear cells, the collection of these cells is invasive. To reduce the donor's burden, we propose the use of urine-derived cells (UDCs), which can be obtained non-invasively from a urine sample. However, the collection of UDCs from elderly donors suffering from age-related diseases such as AD has not been reported, and it is unknown whether these UDCs from the donor aged over 80 years old can be converted into iPSCs and differentiated into neural cells...
2023: Aging brain
Xian Chen, Ling Xie, Ryan Sheehy, Yan Xiong, Adil Muneer, John Wrobel, Kwang-Su Park, Jing Liu, Julia Velez, Yanjia Luo, Ya-Dong Li, Luis Quintanilla, Yongyi Li, Chongchong Xu, Zhexing Wen, Juan Song, Jian Jin, Mohanish Deshmukh
Current amyloid beta-targeting approaches for Alzheimer's disease (AD) therapeutics only slow cognitive decline for small numbers of patients. This limited efficacy exists because AD is a multifactorial disease whose pathological mechanism(s) and diagnostic biomarkers are largely unknown. Here we report a new mechanism of AD pathogenesis in which the histone methyltransferase G9a noncanonically regulates translation of a hippocampal proteome that defines the proteopathic nature of AD. Accordingly, we developed a novel brain-penetrant inhibitor of G9a, MS1262, across the blood-brain barrier to block this G9a-regulated, proteopathologic mechanism...
November 21, 2023: Research Square
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