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Basic Science and Pathogenesis.
Alzheimers Dement
December 2024
David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Background: Progressive supranuclear palsy (PSP) is a neurodegenerative disorder involving pathological deposition of tau that includes glial inclusions and specific regional vulnerability patterns. Therapeutic developments are hampered by incomplete understanding of disease mechanisms. Few studies have examined its cell type-specific effects.
View Article and Find Full Text PDFDescription of changes in chemical bonding along the pathways of chemical reactions by deformation of the molecular electrostatic potential.
J Mol Model
January 2025
Department of Theoretical Chemistry, Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387, Krakow, Poland.
Context: The analysis of the changes in the electronic structure along intrinsic reaction coordinate (IRC) paths for model reactions: (i) ethylene + butadiene cycloaddition, (ii) prototype SN2 reaction Cl + CH3Cl, (iii) HCN/CNH isomerization assisted by water, (iv) CO + HF → C(O)HF was performed, in terms of changes in the deformation density (Δr) and the deformation of MEP (ΔMEP). The main goal was to further examine the utility of the ΔMEP as a descriptor of chemical bonding, and to compare the pictures resulting from Δr and ΔMEP. Both approaches clearly show that the main changes in the electronic structure occur in the TS region.
View Article and Find Full Text PDFBasic Science and Pathogenesis.
Alzheimers Dement
December 2024
Huashan Hospital, Fudan University, Shanghai, Shanghai, China.
Background: Cognition and its two critical proxies, socioeconomic status (SES) and educational attainment (EA), contribute substantially to human health and are heritable. Elucidating the genetic characteristics of SES/EA/Cognition not only helps to understand the innate individual differences in cognition, but also aids in unraveling the biological mechanisms of complex cognitive-related disorders such as Alzheimer's disease (AD). Here, we explored the rare and common protein-coding variants impacting the comprehensive cognition phenotypic spectrum by leveraging large-scale exomes.
View Article and Find Full Text PDFBasic Science and Pathogenesis.
Alzheimers Dement
December 2024
The Jackson Laboratory, Bar Harbor, ME, USA.
Background: Determining the precise genetic mechanisms that contribute to LOAD, both in coding and noncoding variants, will enable a deeper understanding of pathogenesis and advance preclinical models for the testing of targeted therapeutics.
Methods: We have introduced candidate genetic variants in the EPHA1, BIN1, CD2AP, SCIMP, KLOTHO, PTK2B, ADAMTS4, IL1RAP, IL34, and PTPRB loci into a sensitized mouse model already harboring humanized amyloid-beta, APOE4, and Trem2.R47H alleles knocked in to a C57BL/6J background.
Basic Science and Pathogenesis.
Alzheimers Dement
December 2024
Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
Background: Two-thirds of Alzheimer's Disease (AD) cases are women, and our team has identified molecular factors that relate to disease in a sex-specific manner. Here, we leverage single-cell transcriptomics from dorsolateral prefrontal cortex (N = 424) from the Religious Orders Study and Memory and Aging Project (ROS/MAP; AD Knowledge Portal syn2580853) to characterize sex-specific contributors at cellular resolution.
Method: Single-nucleic RNAseq data was generated and processed as previously described.
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