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Background: Convergent evidence indicates that deficits in the endosomal recycling pathway underlies pathogenesis of Alzheimer's disease (AD). SORL1 encodes the retromer-associated receptor SORLA that plays an essential role in recycling of AD-associated cargos such as the amyloid precursor protein and the glutamatergic AMPA receptor. Importantly, loss of function pathogenic SORL1 variants are associated with AD.
View Article and Find Full Text PDFDrug Development.
Alzheimers Dement
December 2024
Keck School of Medicine at University of Southern California, Los Angeles, CA, USA.
Background: ABCA1-mediated cholesterol transport is a central feature in many lipid- dependent diseases including APOE4-associated Alzheimer's disease and atherosclerosis-CVD. ABCA1 upregulation of RNA transcription by nuclear factors (LXR, RXR) have been associated with liver side-effects because of the common promotor element for ABCA1 and Fatty Acid Synthase. The ABCA1 agonist CS6253, derived from the C-terminal of apoE was designed to stabilize and enhance ABCA1 function, thereby providing a safe alternative to transcriptional upregulation.
View Article and Find Full Text PDFDementia Care Research and Psychosocial Factors.
Alzheimers Dement
December 2024
Tohoku University, Sendai, Miyagi, Japan.
Background: Loneliness has been linked to cognitive decline and an elevated risk of Alzheimer's disease (AD). Previous studies measured loneliness at a single point time, which may not accurately capture the longitudinal changes of different loneliness types (e.g.
View Article and Find Full Text PDFDementia Care Practice.
Alzheimers Dement
December 2024
VA Boston Healthcare System, Jamaica Plain, MA, USA.
Background: Mixed dementia type - Alzheimer's Disease (AD), cerebral amyloid angiopathy (CAA), and vascular - is vastly recognized as a cause of dementia in older adults. Whereas CAA, primarily leptomeningeal, is a frequent complication in hereditary transthyretin cardiac amyloidosis (TTRCA), it is unusually reported in association with wild-type TTR, with or without polyneuropathy. The knowledge of mixed dementia and wild-type TTR association is even scarcer.
View Article and Find Full Text PDFCombination Antithrombotic Therapy for Reduction of Recurrent Ischemic Stroke in Intracranial Atherosclerotic Disease.
Stroke
January 2025
Population Health Research Institute, University of British Columbia, Vancouver, Canada. (M.A.S., J.W.E., A.H.K., A. Shoamanesh, A.T., R.G.H., A.C., R.Z.).
Background: Stroke secondary to intracranial atherosclerotic disease (ICAD) is associated with high recurrence risk despite currently available secondary prevention strategies. In patients with systemic atherosclerosis, a significant reduction of stroke risk with no increase in intracranial or fatal hemorrhage was seen when rivaroxaban 2.5 mg twice daily was added to aspirin.
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