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Drug Development.
Alzheimers Dement
December 2024
University of Kentucky Sanders-Brown Center on Aging, Lexington, KY, USA.
Background: The presence of multiple comorbid pathologic features in late-onset dementia has been well documented across cohort studies that incorporate autopsy evaluation. It is likely that such mixed pathology potentially confounds the results of interventional trials that are designed to target a solitary pathophysiologic mechanism in Alzheimer's disease and related dementias (ADRD).
Method: The UK ADRC autopsy database was screened for participants who had previously engaged in therapeutic interventional trials for Alzheimer's disease, vascular cognitive impairment, dementia, and/or ADRD prevention trials from 2005 to the present.
Background: There is an urgent need for new therapeutic and diagnostic targets for Alzheimer's disease (AD). Dementia afflicts roughly 55 million individuals worldwide, and the prevalence is increasing with longer lifespans and the absence of preventive therapies. Given the demonstrated heterogeneity of Alzheimer's disease in biological and genetic components, it is critical to identify new therapeutic approaches.
View Article and Find Full Text PDFUntangling the Genetic Threads of Alzheimer's: Insights into Risk Factors and Biomarkers.
Curr Gene Ther
January 2025
Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.
Dementia is a comprehensive term that refers to illnesses characterized by a decline in cognitive memory and other cognitive functions, affecting a person's overall ability to operate. The exact causes of dementia are unknown to this day. The heterogeneity of Alzheimer's indicates the contribution of genetic polymorphism to this disease.
View Article and Find Full Text PDFSubtypes of Insomnia Disorder Identified by Cortical Morphometric Similarity Network.
Hum Brain Mapp
January 2025
Sleep and NeuroImaging Center, Faculty of Psychology, Southwest University, Chongqing, China.
Insomnia disorder (ID) is a highly heterogeneous psychiatric disease, and the use of neuroanatomical data to objectively define biological subtypes is essential. We aimed to examine the neuroanatomical subtypes of ID by morphometric similarity network (MSN) and the association between MSN changes and specific transcriptional expression patterns. We recruited 144 IDs and 124 healthy controls (HC).
View Article and Find Full Text PDFS6K1 is a Targetable Vulnerability in Tumors Exhibiting Plasticity and Therapy Resistance.
Int J Biol Sci
January 2025
Department of Toxicology and Cancer Biology, College of Medicine, University of Kentucky, Lexington, Kentucky, USA.
Most tumors initially respond to treatment, yet refractory clones subsequently develop owing to resistance mechanisms associated with cancer cell plasticity and heterogeneity. We used a chemical biology approach to identify protein targets in cancer cells exhibiting diverse driver mutations and representing models of tumor lineage plasticity and therapy resistance. An unbiased screen of a drug library was performed against cancer cells followed by synthesis of chemical analogs of the most effective drug.
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