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Drug Development.
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.
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Alzheimers Dement
December 2024
UCSF Weill Institute for Neurosciences, San Francisco, CA, USA.
Background: Efforts to genetically reverse C9orf72 pathology have been hampered by our incomplete understanding of the regulation of this complex locus.
Method: We generated five different genomic excisions at the C9orf72 locus in a patient-derived iPSC line and a WT line (11 total isogenic lines), and examined gene expression and pathological hallmarks of C9 FTD/ALS in motor neurons differentiated from these lines. Comparing the excisions in these isogenic series removed the confounding effects of different genomic backgrounds and allowed us to probe the effects of specific genomic changes.
Background: While a number of recent anti-amyloid antibodies demonstrated a robust reduction of amyloid biomarkers in clinical trials, the impact on functional improvement is much more variable. We hypothesize that this larger variability is driven by comedications, common genotype variants and underlying tau pathology.
Method: In a previously calibrated computational neuroscience model of ADAS-Cog, we implemented the effect of soluble amyloid monomers and oligomers on glutamate and nicotinic AChR neurotransmission and the effect of intracellular tau oligomers on voltage-gated Na and K+ channels and synaptic density.
Dementia Care Research and Psychosocial Factors.
Alzheimers Dement
December 2024
Oregon Health & Science University, Portland, OR, USA.
Background: Current tools to assess caregiver burden in individuals caring for people living with dementia commonly involve the use of questionnaires administered at infrequent intervals. Caregiver burden can vary significantly between individuals and at different time points throughout the progression of the disease. There has been research investigating the determinants of caregiver burden, but less is known about what represents a clinically-meaningful amount of intra-individual change in caregiver burden.
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Alzheimers Dement
December 2024
University of Iowa, Iowa City, IA, USA.
Background: Nursing home (NH) residents with dementia commonly experience mealtime behaviors that negatively impact nutrition and function. Residents do not receive person-centered mealtime care (PCMC) due to multilevel factors one prioritized modifiable factor is lack of effective PCMC programs. This study aimed to develop a PCMC program and test its feasibility, acceptability, usefulness and preliminary efficacy.
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