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Basic Science and Pathogenesis.
Alzheimers Dement
December 2024
Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA.
Article Synopsis
- Asymptomatic Alzheimer's disease (AsymAD) is characterized by the presence of Alzheimer's pathology in individuals who maintain cognitive function, showing lower neuroinflammation compared to symptomatic Alzheimer's disease cases.
- Research using postmortem brain samples revealed that AsymAD subjects have unique characteristics such as enriched core plaques and reduced tau aggregation, along with increased microglial activity around amyloid plaques.
- The study suggests that the composition of the plaque microenvironment, particularly enhanced actin-based motility pathways in microglia, may play a key role in the resilience to Alzheimer's pathology and cognitive decline in AsymAD individuals.
Impact of dementia and mild cognitive impairment on bone health in older people.
Aging Clin Exp Res
December 2024
MRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, UK.
Mild cognitive impairment, dementia and osteoporosis are common diseases of ageing and, with the increasingly ageing global population, are increasing in prevalence. These conditions are closely associated, with shared risk factors, common underlying biological mechanisms and potential direct causal pathways. In this review, the epidemiological and mechanistic links between mild cognitive impairment, dementia and skeletal health are explored.
View Article and Find Full Text PDFHigh-resolution DNA methylation changes reveal biomarkers of heart failure with preserved ejection fraction versus reduced ejection fraction.
Basic Res Cardiol
December 2024
Department of Advanced Medical and Surgical Sciences (DAMSS), University of Campania "Luigi Vanvitelli", 80138, Naples, Italy.
Novel biomarkers are needed to better identify-and distinguish-heart failure with preserved ejection fraction (HFpEF) from other clinical phenotypes. The goal of our study was to identify epigenetic-sensitive biomarkers useful to a more accurate diagnosis of HFpEF. We performed a network-oriented genome-wide DNA methylation study of circulating CD4 T lymphocytes isolated from peripheral blood using reduced representation bisulfite sequencing (RRBS) in two cohorts (i.
View Article and Find Full Text PDFMechanistic Learning for Predicting Survival Outcomes in Head and Neck Squamous Cell Carcinoma.
CPT Pharmacometrics Syst Pharmacol
December 2024
COMPutational Pharmacology and Clinical Oncology Department, Inria Sophia Antipolis - Méditerranée, Cancer Research Center of Marseille, Inserm UMR1068, CNRS UMR7258, Aix Marseille University UM105, Marseille, France.
We employed a mechanistic learning approach, integrating on-treatment tumor kinetics (TK) modeling with various machine learning (ML) models to address the challenge of predicting post-progression survival (PPS)-the duration from the time of documented disease progression to death-and overall survival (OS) in Head and Neck Squamous Cell Carcinoma (HNSCC). We compared the predictive power of model-derived TK parameters versus RECIST and assessed the efficacy of nine TK-OS ML models against conventional survival models. Data from 526 advanced HNSCC patients treated with chemotherapy and cetuximab in the TPExtreme trial were analyzed using a double-exponential model.
View Article and Find Full Text PDFADNP is essential for sex-dependent hippocampal neurogenesis, through male unfolded protein response and female mitochondrial gene regulation.
Mol Psychiatry
December 2024
Elton Laboratory for Molecular Neuroendocrinology, Department of Human Molecular Genetics and Biochemistry, Faculty of Medical and Health Sciences, Adams Super Center for Brain Studies and Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, 6997801, Israel.
Essential for brain formation and protective against tauopathy, activity-dependent neuroprotective protein (ADNP) is critical for neurogenesis and cognitive functions, while regulating steroid hormone biogenesis. As such, de novo mutations in ADNP lead to syndromic autism and somatic ADNP mutations parallel Alzheimer's disease progression. Furthermore, clinical trials with the ADNP fragment NAP (the investigational drug davunetide) showed efficacy in women suffering from the tauopathy progressive supranuclear palsy and differentially boosted memory in men (spatial) and women (verbal), exhibiting prodromal Alzheimer's disease.
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