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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.

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Drug Development.

Alzheimers Dement

December 2024

Virginia Commonwealth University, Richmond, VA, USA.

Background: Pyroptosis is a type of inflammasome-dependent cell death, in which gasdermin D (GSDMD) plays key roles as the executor. Neuroinflammation and pyroptosis have been indicated critical roles in neurodegenerative disorders including Alzheimer's disease (AD). Therefore, novel GSDMD inhibitors represent valuable probes to understand and validate GSDMD as a viable drug target for AD.

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Background: Understanding the fundamental differences between the human and pre-human brain is a prerequisite for designing meaningful models and therapies for AD. Expressed CHRFAM7A, a human restricted gene with carrier frequency of 75% in the human population predicts profound translational significance.

Method: The physiological role of CHRFAM7A in human brain is explored using multiomics approach on 600 post mortem human brain tissue samples (ROSMAP).

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Background: Cognitive decline associated with Alzheimer's disease (AD) correlates with hyperphosphorylated tau (pTau) propagating between neurons along networks connected by synapses. It has been hypothesized this transcellular transmission occurs partially by extracellular vesicles (EVs). Both genetic and pharmacological inhibition of nSMase2 has been found to inhibit EV biogenesis and pTau propagation.

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Background: The National Institute on Aging (NIA) Imbedded Pragmatic Alzheimer's Disease and Alzheimer's Related Dementia (AD/ADRD) Clinical Trials (IMPACT) Collaboratory, in partnership with the Alzheimer's Association, convened a Lived Experience Panel (LEP), a group of 9-12 individuals, including people living with cognitive symptoms, proxies representing people with an advanced cognitive disorder or who are deceased, and care partners of a person living with dementia. The aim was for the LEP members to share their experiences with research, inform the development of research priorities, and provide input on conducting embedded pragmatic clinical trials (ePCTs) of dementia care interventions. Given the importance of providing a space for people with lived experiences to share their thoughts and recommendations, we continue to report on the final stage of LEP in its original design.

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