Use the keywords feature with a free QxMD account.
Use Read by QxMD to access full text via your institution or open access sources.
Read also provides personalized recommendations to keep you up to date in your field.
Existing User
Sign InNew to Read
Sign Up#1
JOURNAL ARTICLE
Rei Murakami, Hirotaka Watanabe, Hideko Hashimoto, Mayu Kashiwagi-Hakozaki, Tadafumi Hashimoto, Celeste M Karch, Takeshi Iwatsubo, Hideyuki Okano
Genetic variants in the apolipoprotein E ( APOE ) gene affect the onset and progression of Alzheimer's disease (AD). The APOE Christchurch ( APOE Ch) variant has been identified as the most prominent candidate for preventing the onset and progression of AD. In this study, we generated isogenic APOE3 Ch/ 3 Ch human induced pluripotent stem cells (iPSCs) from APOE3 / 3 healthy control female iPSCs and induced them into astrocytes. RNA expression analysis revealed the inherent resilience of APOE3 Ch/ 3 Ch astrocytes to induce a reactive state in response to inflammatory cytokines...
April 22, 2024: Journal of Neuroscience
#2
Vasudevan Ramachandran, Nur Afiqah Mohamad, Mohd Nazil Salleh, Wan Aliaa Wan Sulaiman, Liyana Najwa Inche Mat, Mohd Hazmi Mohamed, Ching Siew Mooi, Abdul Hanif Khan Yusof Khan, Hamidon Basri, Pannerselvam Periasamy, Vajiravelu Suganthi, Narenkumar Jayaraman
INTRODUCTION: Vascular dementia (VaD), a neurocognitive impairment directly related to vascular injury, is the second most common cause of age-related dementia. Although numerous studies have investigated candidate genetic polymorphisms associated with VaD in Asia, the genetics of VaD remains unclear. METHODS: This review provides an updated meta-analysis of genetic polymorphisms associated with VaD in Asians, using the PRISMA guidelines. Published literature up to May 2021 was extracted from the PubMed, Scopus, Ovid, and EBSCO host databases...
April 18, 2024: Dementia and Geriatric Cognitive Disorders
#3
JOURNAL ARTICLE
Gregg E Homanics, Jung Eun Park, Lauren Bailey, David J Schaeffer, Lauren Schaeffer, Jie He, Shuoran Li, Tingting Zhang, Annat Haber, Catrina Spruce, Anna Greenwood, Takeshi Murai, Laura Schultz, Lauren Mongeau, Seung-Kwon Ha, Julia Oluoch, Brianne Stein, Sang Ho Choi, Hasi Huhe, Amantha Thathiah, Peter L Strick, Gregory W Carter, Afonso C Silva, Stacey J Sukoff Rizzo
INTRODUCTION: Fundamental questions remain about the key mechanisms that initiate Alzheimer's disease (AD) and the factors that promote its progression. Here we report the successful generation of the first genetically engineered marmosets that carry knock-in (KI) point mutations in the presenilin 1 (PSEN1) gene that can be studied from birth throughout lifespan. METHODS: CRISPR/Cas9 was used to generate marmosets with C410Y or A426P point mutations in PSEN1. Founders and their germline offspring are comprehensively studied longitudinally using non-invasive measures including behavior, biomarkers, neuroimaging, and multiomics signatures...
April 4, 2024: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
#4
JOURNAL ARTICLE
Paula Perez-Corredor, Timothy E Vanderleest, Guido N Vacano, Justin S Sanchez, Nelson D Villalba-Moreno, Claudia Marino, Susanne Krasemann, Miguel A Mendivil-Perez, David Aguillón, Marlene Jiménez-Del-Río, Ana Baena, Diego Sepulveda-Falla, Francisco Lopera, Yakeel T Quiroz, Joseph F Arboleda-Velasquez, Randall C Mazzarino
A patient with the PSEN1 E280A mutation and homozygous for APOE3 Christchurch ( APOE3Ch ) displayed extreme resistance to Alzheimer's disease (AD) cognitive decline and tauopathy, despite having a high amyloid burden. To further investigate the differences in biological processes attributed to APOE3Ch , we generated induced pluripotent stem (iPS) cell-derived cerebral organoids from this resistant case and a non-protected control, using CRISPR/Cas9 gene editing to modulate APOE3Ch expression. In the APOE3Ch cerebral organoids, we observed a protective pattern from early tau phosphorylation...
2024: Frontiers in Molecular Neuroscience
#5
JOURNAL ARTICLE
Therése Klingstedt, Linda Lantz, Hamid Shirani, Junyue Ge, Jörg Hanrieder, Ruben Vidal, Bernardino Ghetti, K Peter R Nilsson
Aggregated species of amyloid-β (Aβ) are one of the pathological hallmarks in Alzheimer's disease (AD), and ligands that selectively target different Aβ deposits are of great interest. In this study, fluorescent thiophene-based ligands have been used to illustrate the features of different types of Aβ deposits found in AD brain tissue. A dual-staining protocol based on two ligands, HS-276 and LL-1, with different photophysical and binding properties, was developed and applied on brain tissue sections from patients affected by sporadic AD or familial AD associated with the PSEN1 A431E mutation...
March 24, 2024: ACS Chemical Neuroscience
#6
JOURNAL ARTICLE
Lan Ma, Xi Zhou, Siyue Yao, Xinyu Zhang, Ji Mao, Barbara Vona, Liwen Fan, Shu Lou, Dandan Li, Lin Wang, Yongchu Pan
Craniofacial malformations, often associated with syndromes, are prevalent birth defects. Emerging evidence underscores the importance of m6 A modifications in various bioprocesses such as stem cell differentiation, tissue development, and tumorigenesis. Here, in vivo, experiments with zebrafish models revealed that mettl3-knockdown embryos at 144 h postfertilization exhibited aberrant craniofacial features, including altered mouth opening, jaw dimensions, ethmoid plate, tooth formation and hypoactive behavior...
March 20, 2024: Cell Death & Disease
#7
JOURNAL ARTICLE
Limin Ma, Fengyu Wang, Shuai Chen, Shenghui Wang, Zhenzhen Wang, Mingrong Xia, Yongli Li, Huimin Ma, Junkui Shang, Jiewen Zhang
Familial Alzheimer's disease (AD) is a rare disease caused by autosomal-dominant mutations. APP (encoding amyloid precursor protein), PSEN1 (encoding presenilin 1), and PSEN2 (encoding presenilin 2) are the most common genes cause dominant inherited AD. This study aimed to demonstrate a Chinese early-onset AD pedigree presenting as progressive memory impairment, apraxia, visual-spatial disorders, psychobehavioral disorders, and personality changes with a novel APP gene mutation. The family contains four patients, three carries and three normal family members...
March 19, 2024: Neuromolecular Medicine
#8
JOURNAL ARTICLE
Yanmei Qi, Xu Wang, Xihan Guo
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid beta (Aβ) in brain. Mounting evidence has revealed critical roles of microRNAs (miRNAs) in AD pathogenesis; however, the miRNAs directly targeting presenilin1 ( PSEN1 ), which encodes the catalytic core subunit of γ-secretase that limits the production of Aβ from amyloid precursor protein (APP), are extremely understudied. The present study aimed to identify miRNAs targeting PSEN1 and its effect on Aβ production...
2024: Frontiers in Aging Neuroscience
#9
JOURNAL ARTICLE
Annu Grewal, Deepak Sheokand, Raveena Chauhan, Vandana Saini, Ajit Kumar
Alzheimer's disease (AD) is the leading cause of dementia worldwide with therapeutic lacunae till date. The beta-amyloid (Aβ) accumulation triggers AD pathogenesis, though clinical trials lowering Aβ have not altered disease outcomes suggesting other interacting factors to be identified for drug design of AD. Therefore, it is of interest to identify potential hub proteins interlinked with disease-driving pathways using a network-based approach for AD therapeutic designing. Literature mining was done to identify proteins implicated in AD etiology...
2024: Bioinformation
#10
REVIEW
Harkomal Verma, Sharanjot Kaur, Sukhchain Kaur, Prabhakar Gangwar, Monisha Dhiman, Anil Kumar Mantha
Alzheimer's disease (AD), a multifactorial disease, is characterized by the accumulation of neurofibrillary tangles (NFTs) and amyloid beta (Aβ) plaques. AD is triggered via several factors like alteration in cytoskeletal proteins, a mutation in presenilin 1 (PSEN1), presenilin 2 (PSEN2), amyloid precursor protein (APP), and post-translational modifications (PTMs) in the cytoskeletal elements. Owing to the major structural and functional role of cytoskeletal elements, like the organization of axon initial segmentation, dendritic spines, synaptic regulation, and delivery of cargo at the synapse; modulation of these elements plays an important role in AD pathogenesis; like Tau is a microtubule-associated protein that stabilizes the microtubules, and it also causes inhibition of nucleo-cytoplasmic transportation by disrupting the integrity of nuclear pore complex...
March 16, 2024: Molecular Neurobiology
#11
JOURNAL ARTICLE
Carmen Romero-Molina, Sarah M Neuner, Marcelina Ryszawiec, Alice Pébay, Dominantly Inherited Alzheimer Network, Edoardo Marcora, Alison Goate
Several genetic variants that affect microglia function have been identified as risk factors for Alzheimer's Disease (AD), supporting the importance of this cell type in disease progression. However, the effect of autosomal dominant mutations in the amyloid precursor protein ( APP ) or the presenilin ( PSEN1/2 ) genes has not been addressed in microglia in vivo. We xenotransplanted human microglia derived from non-carriers and carriers of autosomal dominant AD (ADAD)-causing mutations in the brain of hCSF1 WT or 5XFAD mice...
February 22, 2024: International Journal of Molecular Sciences
#12
JOURNAL ARTICLE
Khaled S Abd-Elrahman, Tash-Lynn L Colson, Shaarika Sarasija, Stephen S G Ferguson
Alzheimer's disease (AD) is the most prevalent type of dementia, disproportionately affecting females, who make up nearly 60% of diagnosed cases. In AD patients, the accumulation of beta-amyloid (Aβ) in the brain triggers a neuroinflammatory response driven by neuroglia, worsening the condition. We have previously demonstrated that VU0486846, an orally available positive allosteric modulator (PAM) targeting M1 muscarinic acetylcholine receptors, enhances cognitive function and reduces Aβ pathology in female APPswe/PSEN1ΔE9 (APP/PS1) mice...
April 2024: Biomedicine & Pharmacotherapy
#13
JOURNAL ARTICLE
Diego Sepulveda-Falla, Jorge I Vélez, Natalia Acosta-Baena, Ana Baena, Sonia Moreno, Susanne Krasemann, Francisco Lopera, Claudio A Mastronardi, Mauricio Arcos-Burgos
INTRODUCTION: Rate of cognitive decline (RCD) in Alzheimer's disease (AD) determines the degree of impairment for patients and of burden for caretakers. We studied the association of RCD with genetic variants in AD. METHODS: RCD was evaluated in 62 familial AD (FAD) and 53 sporadic AD (SAD) cases, and analyzed by whole-exome sequencing for association with common exonic functional variants. Findings were validated in post mortem brain tissue. RESULTS: One hundred seventy-two gene variants in FAD, and 227 gene variants in SAD associated with RCD...
March 7, 2024: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
#14
JOURNAL ARTICLE
Maria Camila Almeida, Sarah J Eger, Caroline He, Morgane Audouard, Arina Nikitina, Stella M K Glasauer, Dasol Han, Barbara Mejía-Cupajita, Juliana Acosta-Uribe, Nelson David Villalba-Moreno, Jessica Lisa Littau, Megan Elcheikhali, Erica Keane Rivera, Daniel Carneiro Carrettiero, Carlos Andrés Villegas-Lanau, Diego Sepulveda-Falla, Francisco Lopera, Kenneth S Kosik
Highly penetrant autosomal dominant Alzheimer's disease (ADAD) comprises a distinct disease entity as compared to the far more prevalent form of AD in which common variants collectively contribute to risk. The downstream pathways that distinguish these AD forms in specific cell types have not been deeply explored. We compared single-nucleus transcriptomes among a set of 27 cases divided among PSEN1-E280A ADAD carriers, sporadic AD, and controls. Autophagy genes and chaperones clearly defined the PSEN1-E280A cases compared to sporadic AD...
February 21, 2024: Neuron
#15
JOURNAL ARTICLE
Tingting Shen, Jiucheng Shi, Xijuan Zhao, Li Fu, Na Wang, Jiaxin Han, Xiaodong Zheng, Yingli Chen, Minghui Li, Cui Ma, Pixu Liu, Daling Zhu
Small muscular pulmonary artery remodeling is a dominant feature of PAH. PSEN1 affects angiogenesis, cancer and Alzheimer's disease. We aimed to determine the role of PSEN1 in the pathogenesis of vascular remodeling in PH. Haemodynamics and vascular remodeling in the Psen1 -knockin and smooth muscle-specific Psen1 -knockout mice were assessed. The functional partners of PSEN1 were predicted by bioinformatics analysis and biochemical experiments. The therapeutic effect of PH was evaluated by administration of the PSEN1-specific inhibitor ELN318463...
February 21, 2024: American Journal of Respiratory Cell and Molecular Biology
#16
JOURNAL ARTICLE
Nelly Joseph-Mathurin, Rebecca L Feldman, Ruijin Lu, Zahra Shirzadi, Carmen Toomer, Junie R Saint Clair, Yinjiao Ma, Nicole S McKay, Jeremy F Strain, Collin Kilgore, Karl A Friedrichsen, Charles D Chen, Brian A Gordon, Gengsheng Chen, Russ C Hornbeck, Parinaz Massoumzadeh, Austin A McCullough, Qing Wang, Yan Li, Guoqiao Wang, Sarah J Keefe, Stephanie A Schultz, Carlos Cruchaga, Gregory M Preboske, Clifford R Jack, Jorge J Llibre-Guerra, Ricardo F Allegri, Beau M Ances, Sarah B Berman, William S Brooks, David M Cash, Gregory S Day, Nick C Fox, Michael Fulham, Bernardino Ghetti, Keith A Johnson, Mathias Jucker, William E Klunk, Christian la Fougère, Johannes Levin, Yoshiki Niimi, Hwamee Oh, Richard J Perrin, Gerald Reischl, John M Ringman, Andrew J Saykin, Peter R Schofield, Yi Su, Charlene Supnet-Bell, Jonathan Vöglein, Igor Yakushev, Adam M Brickman, John C Morris, Eric McDade, Chengjie Xiong, Randall J Bateman, Jasmeer P Chhatwal, Tammie L S Benzinger
INTRODUCTION: Amyloidosis, including cerebral amyloid angiopathy, and markers of small vessel disease (SVD) vary across dominantly inherited Alzheimer's disease (DIAD) presenilin-1 (PSEN1) mutation carriers. We investigated how mutation position relative to codon 200 (pre-/postcodon 200) influences these pathologic features and dementia at different stages. METHODS: Individuals from families with known PSEN1 mutations (n = 393) underwent neuroimaging and clinical assessments...
February 21, 2024: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
#17
JOURNAL ARTICLE
Kellie Benzow, Kul Karanjeet, Adrian L Oblak, Gregory W Carter, Michael Sasner, Michael D Koob
INTRODUCTION: Genetic studies conducted over the past four decades have provided us with a detailed catalog of genes that play critical roles in the etiology of Alzheimer's disease (AD) and related dementias (ADRDs). Despite this progress, as a field we have had only limited success in incorporating this rich complexity of human AD/ADRD genetics findings into our animal models of these diseases. Our primary goal for the gene replacement (GR)-AD project is to develop mouse lines that model the genetics of AD/ADRD as closely as possible...
February 11, 2024: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
#18
JOURNAL ARTICLE
Lory J Rochín-Hernández, Lory S Rochín-Hernández, Mayte L Padilla-Cristerna, Andrea Duarte-García, Miguel A Jiménez-Acosta, María P Figueroa-Corona, Marco A Meraz-Ríos
Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the predominant form of dementia globally. No reliable diagnostic, predictive techniques, or curative interventions are available. MicroRNAs (miRNAs) are vital to controlling gene expression, making them valuable biomarkers for diagnosis and prognosis. This study examines the transcriptome of olfactory ecto-mesenchymal stem cells (MSCs) derived from individuals with the PSEN1(A431E) mutation (Jalisco mutation). The aim is to determine whether this mutation affects the transcriptome and expression profile of miRNAs and their target genes at different stages of asymptomatic, presymptomatic, and symptomatic conditions...
January 27, 2024: International Journal of Molecular Sciences
#19
Nicholas Schultheis, Alyssa Connell, Alexander Kapral, Robert J Becker, Richard Mueller, Shalini Shah, Mackenzie O'Donnell, Matthew Roseman, Weihua Wang, Fei Yin, Ryan Weiss, Scott B Selleck
Mutations in presenilin-1 (PSEN1) are the most common cause of familial, early-onset Alzheimer's disease (AD), typically producing cognitive deficits in the fourth decade. A variant of APOE, APOE3 Christchurch (APOE3ch) , was found associated with protection from both cognitive decline and Tau accumulation in a 70-year-old bearing the disease-causing PSEN1-E280A mutation. The amino acid change in ApoE3ch is within the heparan sulfate (HS) binding domain of APOE, and purified APOEch showed dramatically reduced affinity for heparin, a highly sulfated form of HS...
January 24, 2024: bioRxiv
#20
JOURNAL ARTICLE
Wojciech Michno, Andrew Bowman, Durga Jha, Karolina Minta, Junyue Ge, Srinivas Koutarapu, Henrik Zetterberg, Kaj Blennow, Tammaryn Lashley, Ron M A Heeren, Jörg Hanrieder
Lipid dysregulations have been critically implicated in Alzheimer's disease (AD) pathology. Chemical analysis of amyloid-β (Aβ) plaque pathology in transgenic AD mouse models has demonstrated alterations in the microenvironment in the direct proximity of Aβ plaque pathology. In mouse studies, differences in lipid patterns linked to structural polymorphism among Aβ pathology, such as diffuse, immature, and mature fibrillary aggregates, have also been reported. To date, no comprehensive analysis of neuronal lipid microenvironment changes in human AD tissue has been performed...
February 1, 2024: ACS Chemical Neuroscience
Make the most of Read.
Download the mobile app.
Download the mobile app.
Fetching more papers... 
