Developing Small Molecules that Restore Gamma Brain Rhythms in Alzheimer’s Disease
Dr. Istvan Mody, Tony Coelho Chair in Neurology and Professor of Neurology, and Dr. Varghese John, Professor of Neurology and Director of the UCLA Neurology Drug Discovery Laboratory (DDL), continue their collaboration through the philanthropic support of the Easton Center, to develop small molecules that can restore damaged brain rhythms in patients suffering from Alzheimer’s disease (AD). Their goal is to validate the effectiveness of a new chemical entity that the team has developed in a mouse model of Alzheimer’s disease and ultimately proceed to human studies by increasing neural oscillations in gamma frequencies and improving the cognitive performance of dementia patients.
Reprogramming Neuroimmune Signaling to Improve Brain Function in Dementia
Dr. Jessica Rexach, John Douglas French Alzheimer’s Foundation Endowed Chair and Assistant Professor of Neurology, and Dr. Ranmal Samarasinghe, Assistant Professor of Neurology, thanks to the philanthropic support through the Easton Center, are developing a novel human multicellular stem-cell platform to study neuroimmune circuit dysfunction and discover new drugs. This collaboration utilizes a stem-cell model of tauopathy developed by the Samarasinghe group. The project will determine the impact of microglial neuroimmune signaling on hippocampal circuit activity in a tauopathy model.
Exploring Molecular Mechanisms for Pathological Tau Transmission in Alzheimer’s Disease
Dr. Chao Peng, Assistant Professor of Neurology, and his team are identifying the intercellular transmission and subsequent amplification of tau in Alzheimer’s disease and related disorders. With the support of philanthropy through the Easton Center, the group will be able to capture proteins transiently interacting with tau and identify indirect binding partners. These findings will be a key to developing novel therapies targeting genes to slow Alzheimer’s progression.
Identifying and Treating Epilepsy and Epileptic Activity in Alzheimer’s Disease
Dr. Keith Vossel pioneered the first overnight electroencephalogram (EEG) and one-hour magnetoencephalography (MEG) study to identify silent epileptic activity in 42 percent of patients with Alzheimer’s disease. His team demonstrated that silent epileptic activity, usually occurring during sleep, accelerates the decline in cognitive function in patients with Alzheimer’s disease. With the support of philanthropy through the Easton Center, Dr. Vossel will advance the study with colleagues in the UCLA Adult Epilepsy Program to develop neurophysiological biomarkers to diagnose epileptic activity in patients with Alzheimer’s disease.
Advanced Data Management and Statistical Core
The ADRC database consists of multiple data elements housed in individual datasets stored using REDCap software. REDCap is a HIPAA-compliant web application that provides high-level data security, audit trails, onsite and offsite backups, and real-time data entry validation. It is trusted by universities across the nation. With the support of Easton Center philanthropy, our highly qualified team, led by Dr. David Elashoff and Jenny Brook, has built and archived historical data collected from the early days of the UCLA ADRC and ongoing studies for the National Alzheimer’s Coordinating Center (NACC) project and other national consortia.
Innovative ADRC Brain Bank
Dr. Shino Magaki, an Assistant Professor of Neuropathology, and Dr. Harry Vinters, a Distinguished Professor of Pathology and Laboratory Medicine, have successfully revised their sampling protocol and have been processing the collected neurodegenerative disease brains donated to the UCLA ADRC Brain Bank housed in a new, modern, sterile facility, thanks to the philanthropic support through the Easton Center. The facility now has a state-of-the-art cryogenic -160˚C freezer for rapidly cooling tissue, with an ultralow -80˚C freezer to be installed for storage, with an emergency backup power source, as the specimens are irreplaceable. The neuropathology team has also performed a thorough inventory of archival brain specimens to add to the UCLA ADRC’s new biorepository database in REDCap.
To make the ADRC Brain Bank even more impactful, Dr. Magaki and Dr. Vinters have been sharing and providing hundreds of grams of frozen, unstained, and stained formalin-fixed paraffin-embedded sections from brains with the neurodegenerative disease to the laboratories in neurology, biochemistry, molecular and medical pharmacology, bioscience, dentistry, and others at UCLA and outside institutions, including Loma Linda University and the University of Kansas. Dr. Magaki and Dr. Vinters are grateful to have the opportunity to expand the collection and distribution of biospecimens and enhance the operations and services of the ADRC Brain Bank.