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Background: The autophagy lysosomal pathway (ALP) and the ubiquitin-proteasome system (UPS) are key proteostasis mechanisms in cells, which are dysfunctional in AD and linked to protein aggregation and neuronal death. Autophagy is over activated in Alzheimer's disease brain whereas UPS is severely impaired. Activating autophagy has received most attention, however recent evidence suggests that UPS can clear aggregate proteins and a potential therapeutic target for AD and protein misfolding diseases.
View Article and Find Full Text PDFDrug Development.
Alzheimers Dement
December 2024
Indiana University School of Medicine, Indianapolis, IN, USA.
Background: Focusing on novel AD treatments, the TREAT-AD centers offer an array of free research tools, shared via the AD Knowledge Portal in a Target Enablement Package (TEP). This abstract showcases the research conducted by the IUSM-Purdue TREAT-AD Center, specifically focusing on Targeting class-II PI3K's as a potential breakthrough in AD therapy. Endocytosis within the brain encompasses diverse pathways for internalizing extracellular cargoes and receptors into cells.
View Article and Find Full Text PDFBackground: Early-onset Alzheimer's disease (EOAD) associated with amyloid precursor protein (APP) duplications or presenilin (PSEN) variants increases risk of seizures. Targeting epileptiform activity with antiseizure medicine (ASM) administration to AD patients may beneficially attenuate cognitive decline (Vossel et al, JAMA Neurology 2021). However, whether mechanistically distinct ASMs differentially suppress seizures in discrete EOAD models is understudied (Lehmann et al, Neurochem Res 2021).
View Article and Find Full Text PDFDementia Care Research and Psychosocial Factors.
Alzheimers Dement
December 2024
Memory and Aging Center, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
Background: Many treatments targeting frontotemporal lobar degeneration (FTLD) are in the developmental pipeline, but the rarity of the disease, coupled with the behavioral and motor features of FTLD, make it challenging to identify sufficient trial participants who can attend frequent in-person visits. Decentralized clinical trial designs with remote evaluations are attractive alternatives but require validated tools for symptom tracking. Our previous cross-sectional analyses showed that cognitive tasks deployed via the ALLFTD Mobile App are reliable and sensitive to early stages of disease.
View Article and Find Full Text PDFDementia Care Research and Psychosocial Factors.
Alzheimers Dement
December 2024
North Bristol NHS Trust, Bristol, United Kingdom.
Background: Poor sleep is associated with neurodegenerative diseases underlying dementia and mild cognitive impairment (MCI), including Alzheimer's disease (AD) and Lewy body disease (LBD). Performing assessments within clinical or laboratory settings may influence validity, however feasibility of home sleep and memory assessments in this population is currently undetermined. This study aimed to identify whether remote home-based sleep and memory research including wearable technology was feasible in older adults with MCI and dementia.
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