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Basic Science and Pathogenesis.
Alzheimers Dement
December 2024
Columbia University, New York, NY, USA.
Background: Alzheimer's disease (AD) missing heritability remains extensive despite numerous genetic risk loci identified by genome-wide association or sequencing studies. This has been attributed, at least partially, to mechanisms not currently investigated by traditional single-marker/gene approaches. Polygenic Risk Scores (PRS) aggregate sparse genetic information across the genome to identify individual genetic risk profiles for disease prediction and patient risk stratification.
View Article and Find Full Text PDFBasic Science and Pathogenesis.
Alzheimers Dement
December 2024
UNC Chapel Hill, Chapel Hill, NC, USA.
Background: In the last decade, we have demonstrated that the brain-enriched E3 ubiquitin ligase TRIM9 regulates cytoskeletal dynamics, membrane remodeling, and netrin-dependent signaling pathways in all stages of neuron development, including the maturation of dendritic spines and electrophysiological activity. Moreover, TRIM9 protein levels increase in the adult brain and are maintained throughout adulthood. In the adult mouse TRIM9 is enriched within the postsynaptic density (PSD), a proteinaceous rich region in the post synapse, containing neurotransmitter receptors, scaffolding proteins, and cytoskeletal elements.
View Article and Find Full Text PDFBasic Science and Pathogenesis.
Alzheimers Dement
December 2024
Centre for Healthy Brain Ageing (CHeBA), University of New South Wales, UNSW Sydney, NSW, Australia.
Background: Subjective Cognitive Complaints (SCCs) can often precede mild cognitive impairment and dementia longitudinally. While increasingly considered an early prodromal stage of dementia, SCCs can also be a symptom of depression. Previous research found that SCCs in the absence of cognitive impairment, controlling for symptoms of depression, were moderately heritable and genetically associated with memory.
View Article and Find Full Text PDFBasic Science and Pathogenesis.
Alzheimers Dement
December 2024
Université de Montpellier, Montpellier, France.
Background: Protein metabolism and turnover can be monitored using tracer methods, notably stable isotope labeling kinetics (SILK) based on 13C-leucine incorporation. This approach has been used in Alzheimer's disease, specifically analyzing the turnover in cerebrospinal fluid of biomarkers of interest, including amyloid peptides, leading to major pathophysiological insights (Nature medicine 12:856-861). This was achieved using immunoprecipitation mass spectrometry, which enables to track a small number of targets present in low concentration.
View Article and Find Full Text PDFBackground: Interventional trials in Alzheimer's Disease (AD) are increasingly targeting early disease stages. To optimize the likelihood of successful outcomes for these trials, there is an important need for tools capable of identifying individuals prone to exhibit clinical progression throughout the course of the trial. The Expanded Brief Assessment of Cognition (Expanded-BAC) and the Virtual Reality Functional Capacity Assessment Tool - Short List (VRFCAT-SLx) are two computerized tests assessing cognitive and functional abilities, respectively.
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