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Amyloid-β deposition in basal frontotemporal cortex is associated with selective disruption of temporal mnemonic discrimination.
J Neurosci
January 2025
Department of Neurobiology and Behavior and Center for the Neurobiology of Learning and Memory, University of California, Irvine, Irvine, California 92697 USA
Cerebral amyloid-beta (Aβ) accumulation, a hallmark pathology of Alzheimer's disease (AD), precedes clinical impairment by two to three decades. However, it is unclear whether Aβ contributes to subtle memory deficits observed during the preclinical stage. The heterogenous emergence of Aβ deposition may selectively impact certain memory domains, which rely on distinct underlying neural circuits.
View Article and Find Full Text PDFPerspective: Minimally clinically important "symptomatic" benefit associated with disease modification resulting from anti-amyloid immunotherapy.
Alzheimers Dement (N Y)
January 2025
Unlabelled: Despite some skepticism regarding the amyloid hypothesis, there is growing evidence that clearing amyloid by targeting specific species of amyloid (plaque, oligomers, fibrils, and protofibrils) for removal has therapeutic benefits. Specifically, there is growing evidence that, in mild cognitive impairment and mild dementia due to Alzheimer's disease (AD), robust and aggressive removal of amyloid can slow cognitive decline as measured by global instruments, composite measures, and cognitive testing. Furthermore, clinical efficacy signals coupled with clear biomarker changes provide the first evidence of disease modification.
View Article and Find Full Text PDFNanostructural Modulation of G-Quadruplex DNA in Neurodegeneration: Orotate Interaction Revealed Through Experimental and Computational Approaches.
J Neurochem
January 2025
Institute of Biostructures and Bioimaging, Italian National Council for Research (IBB-CNR), Naples, Italy.
The natural compound orotic acid and its anionic form, orotate, play a pivotal role in various biological processes, serving as essential intermediates in pyrimidine de novo synthesis, with demonstrated connections to dietary, supplement, and neurodrug applications. A novel perspective on biomolecular aggregation at the nanoscale, particularly pertinent to neurodegeneration, challenges the established paradigm positing that peptide (amyloid beta) and protein (tau) aggregation mainly govern the molecular events underlying prevalent neuropathologies. Emerging biological evidence indicates a notable role for G-quadruplex (G4) DNA aggregation in neurodegenerative processes affecting neuronal cells, particularly in the presence of extended (GC) repeats in nuclear DNA sequences.
View Article and Find Full Text PDFSerum β-secretase 1 (sBACE1) activity in subjective cognitive decline: an exploratory study.
Geroscience
January 2025
Department of Translational Medicine and for Romagna, Università of Ferrara, Via Luigi Borsari 46, 44121, Ferrara, Italy.
β-Secretase-1 (BACE1) plays a key role in the regulation of cerebral amyloid-β homeostasis, being involved in amyloidogenic and, as recently found, amyloidolytic pathways. Growing evidence indicates that increased serum BACE1 (sBACE1) activity might represent an early biomarker for Alzheimer's disease. Here, we tested the hypothesis that an increase in sBACE1 activity may already occur in individuals with subjective cognitive decline (SCD).
View Article and Find Full Text PDFDrug repurposing using artificial intelligence, molecular docking, and hybrid approaches: A comprehensive review in general diseases vs Alzheimer's disease.
Comput Methods Programs Biomed
January 2025
Bioinformatics Programme, Institute of Biological Sciences, Faculty of Science, Universiti Malaya, Kuala Lumpur 50603, Malaysia; Centre of Research in System Biology, Structural, Bioinformatics and Human Digital Imaging (CRYSTAL), Universiti Malaya, Kuala Lumpur 50603, Malaysia. Electronic address:
Background: Alzheimer's disease (AD), the most prevalent form of dementia, remains enigmatic in its origins despite the widely accepted "amyloid hypothesis," which implicates amyloid-beta peptide aggregates in its pathogenesis and progression. Despite advancements in technology and healthcare, the incidence of AD continues to rise. The traditional drug development process remains time-consuming, often taking years to bring an AD treatment to market.
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