ArticleJournal of neurochemistry2021
Alzheimer's protection effect of A673T mutation may be driven by lower Aβ oligomer binding affinity.
Article in Journal of neurochemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- Phase 2 study of zervimesine (CT1812) in participants with mild-to-moderate dementia with Lewy bodies (DLB).Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Trial
- Preclinical and clinical biomarker studies of CT1812: A novel approach to Alzheimer's disease modification.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2021Trial
- Veraguamide E, a Marine Cyanobacterial Depsipeptide Targeting σJournal of natural products · 2025Article
- Nanomaterials in targeting amyloid-β oligomers: current advances and future directions for Alzheimer's disease diagnosis and therapy.Beilstein journal of nanotechnology · 2025Review
- Sigma-2 Receptors-From Basic Biology to Therapeutic Target: A Focus on Age-Related Degenerative Diseases.International journal of molecular sciences · 2023Review
- Development of Fluorescent 4-[4-(3Journal of medicinal chemistry · 2023Article
- Extracellular Amyloid β-protein (1-42) Oligomers Anchor Brain Cells and Make them inert as an Unconventional Integrin-Coupled Ligand.Cellular and molecular neurobiology · 2023Article
- Differentiation of subnucleus-sized oligomers and nucleation-competent assemblies of the Aβ peptide.Biophysical journal · 2023Article
- Emerging Alzheimer's disease therapeutics: promising insights from lipid metabolism and microglia-focused interventions.Frontiers in aging neuroscience · 2023Review
- The Allosteric Antagonist of the Sigma-2 Receptors-Elayta (CT1812) as a Therapeutic Candidate for Mild to Moderate Alzheimer's Disease: A Scoping Systematic Review.Life (Basel, Switzerland) · 2022Article
- Exploring the Involvement of the Amyloid Precursor Protein A673T Mutation against Amyloid Pathology and Alzheimer's Disease in Relation to Therapeutic Editing Tools.Pharmaceutics · 2022Review
- Discovery of Investigational Drug CT1812, an Antagonist of the Sigma-2 Receptor Complex for Alzheimer's Disease.ACS medicinal chemistry letters · 2021Article
- The Protective A673T Mutation of Amyloid Precursor Protein (APP) in Alzheimer's Disease.Molecular neurobiology · 2021Review
- Nutraceutical and Probiotic Approaches to Examine Molecular Interactions of the Amyloid Precursor Protein APP inInternational journal of molecular sciences · 2021Review
- Neurotoxic Soluble Amyloid Oligomers Drive Alzheimer's Pathogenesis and Represent a Clinically Validated Target for Slowing Disease Progression.International journal of molecular sciences · 2021Review
- Alzheimer's protection effect of A673T mutation may be driven by lower Aβ oligomer binding affinity.Journal of neurochemistry · 2021Article
- PGRMC Proteins Are Coming of Age: A Special Issue on the Role of PGRMC1 and PGRMC2 in Metabolism and Cancer Biology.Cancers · 2021Article
- Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Several mutations conferring protection against Alzheimer's disease (AD) have been described, none as profound as the A673T mutation, where carriers are four times less likely to get AD compared to noncarriers. This mutation results in reduced amyloid beta (Aβ) protein production in vitro and lower lifetime Aβ concentration in carriers. Better understanding of the protective mechanisms of the mutation may provide important insights into AD pathophysiology and identify productive therapeutic intervention strategies for disease modification. Aβ(1-42) protein forms oligomers that bind saturably to a single receptor site on neuronal synapses, initiating the downstream toxicities observed in AD. Decreased formation, toxicity, or stability of soluble Aβ oligomers, or reduction of synaptic binding of these oligomers, may combine with overall lower Aβ concentration to underlie A673T's disease protecting mechanism. To investigate these possibilities, we compared the formation rate of soluble oligomers made from Icelandic A673T mutant and wild type (wt) Aβ(1-42) synthetic protein, the amount and intensity of oligomer bound to mature primary rat hippocampal/cortical neuronal synapses, and the potency of bound oligomers to impact trafficking rate in neurons in vitro using a physiologically relevant oligomer preparation method. At equal protein concentrations, mutant protein forms approximately 50% or fewer oligomers of high molecular weight (>50 kDa) compared to wt protein. Mutant oligomers are twice as potent at altering the cellular vesicle trafficking rate as wt at equivalent concentrations, however, mutant oligomers have a >4-fold lower binding affinity to synaptic receptors (K
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.