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http://dx.doi.org/10.1111/bcp.13878 | DOI Listing |
Alzheimers Dement
December 2024
EQT Life Sciences Partners, Amsterdam, 1071 DV Amsterdam, Netherlands.
Background: Alzheimer's disease (AD) trials report a high screening failure rate (potentially eligible trial candidates who do not meet inclusion/exclusion criteria during screening) due to multiple factors including stringent eligibility criteria. Here, we report the main reasons for screening failure in the 12-week screening phase of the ongoing evoke (NCT04777396) and evoke+ (NCT04777409) trials of semaglutide in early AD.
Method: Key inclusion criteria were age 55-85 years; mild cognitive impairment due to AD (Clinical Dementia Rating [CDR] global score of 0.
Alzheimers Dement
December 2024
Washington University School of Medicine, St. Louis, MO, USA.
Background: Alzheimer's disease neuropathology involves the deposition in brain of aggregates enriched with microtubule-binding-region (MTBR) of tau adopting an abnormal conformation between residues 306-378 in the core of aggregates. Anti-tau drugs targeting around this domain have the potential to interfere with the cell-to-cell propagation of pathological tau. Bepranemab is a humanized monoclonal Ig4 antibody binding to tau residues 235-250.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
ADEL Institute of Science & Technology (AIST), ADEL, Inc., Seoul, Korea, Republic of (South).
Background: Abnormal aggregation and accumulation of tau is a hallmark of tauopathy including Alzheimer's disease. Effective targeting of tau for therapeutic purposes requires a clear understanding of its epitope landscape with identification of a key pathogenic tau species. Despite numerous proposed and tested tau epitopes, ranging from the N-terminus to the microtubule-binding region and C-terminus, the most effective target remains elusive.
View Article and Find Full Text PDFBackground: Small, soluble oligomers, rather than mature fibrils, are the major neurotoxic agents in Alzheimer's disease (AD). In the last few years, Aprile and co-workers designed and purified a single-domain antibody (sdAb), called DesAb-O, with high specificity for Aβ oligomeric conformers. Recently, Cascella and co-workers showed that DesAb-O can selectively detect synthetic Aβ oligomers both in vitro and in cultured cells, neutralizing their associated neuronal dysfunction.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Background: Genome-wide association studies (GWAS) have identified close to one hundred loci associated with Alzheimer's disease (AD) risk. However, for most of these loci we do not understand the underlying mechanism leading to disease. Crispr genome editing in human induced pluripotent stem cells (hiPSCs) provides a model system to study the effects of these genetic variants in a disease relevant cell type.
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