Giulio Taglialatela, PhD, and Balaji Krishnan, PhD
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Giulio Taglialatela, PhD, earned his doctorate from the University of Rome La Sapienza in Italy, followed by postdoctoral training at the University of Texas Medical Branch (UTMB), Galveston, Texas, in the Department of Biochemistry & Molecular Biology (BMB) from 1988 to 1990. He returned to UTMB in 1993 as a research assistant professor and rose through the ranks to his appointment as a tenured professor in the Department of Neuroscience & Cell Biology in 2011. In 2014, Dr. Taglialatela became the vice chair for research of the Department of Neurology and the director of the UTMB Mitchell Center for Neurodegenerative Diseases and was endowed as the Lawrence J. Del Papa Distinguished Chair in Neurodegenerative Disease Research. While maintaining a continuously NIH-funded research laboratory over the past 25+ years, Dr. Taglialatela has published over 100 peer-reviewed papers and delivered invited talks at national and international institutions and scientific meetings. He has served on several national and international grant review panels and as a permanent appointed member and chair of the Clinical Neuroscience & Neurodegeneration study section at the National Institutes of Health. For the past decade, Dr. Taglialatela’s main research focus has been to determine the molecular basis of brain/cognitive resilience in the face of AD pathology and to explore approaches to induce such resistance in anyone affected by the disease as a novel therapeutic concept.
Balaji Krishnan, PhD, is a primary faculty member in the Mitchell Center for Neurodegenerative Diseases, Neurology Department at the University of Texas Medical Branch, Galveston, TX. His research focuses on synaptic mechanisms associated with health and disease. He obtained his bachelor’s and master’s degrees from University of Mumbai. During his master’s tenure, he gained expertise in learning behavior, electrophysiology, and molecular biology in the neurogenetics of smell. He employed his expertise in electrophysiological approaches to elucidate the functional signaling mechanisms that are associated with circadian rhythms associated with the sensory system of smell in the fruit fly for his PhD dissertation. The significance of this research was recognized in his first authorship in two papers published in Nature, one of which was in collaboration with Jeffrey Hall, one of the Nobel Laureates (2017) for mechanisms of circadian rhythms. Dr. Krishnan then developed his postdoctoral work on phospholipase D (PLD) signaling mechanisms in associative memory mechanisms in neuropsychiatric disorders. His lab is currently exploring the therapeutic potential associated with modulating PLD signaling to prevent the progression of cognitive decline. Since joining the Mitchell Center for Neurodegenerative Diseases, he has been employing his out-of-the-box thinking and collaborative team efforts in developing and employing functional approaches in rodent models and human clinical samples in elucidating mechanisms of cognitive function important in health and disease.
Importance of Published Article
The existence of individuals who remain cognitively intact despite the presence of neuropathology normally associated with fully symptomatic AD suggests that there is an intrinsic way for the human brain to resist (or significantly delay) the events that lead to cognitive impairment in AD. Understanding the involved cellular mechanism(s) would thus reveal a very effective target to develop a novel therapeutic concept for AD centered on inducing cognitive resistance in affected patients. Such therapy is expected to be effective in humans, as demonstrated by the existence of these resilient individuals.
With this goal in mind, the paper “Functional integrity of synapses in the central nervous system of cognitively intact individuals with high Alzheimer’s neuropathology is associated with absence of synaptic tau oligomers” (J Alzheimers Dis 78, 1661-1678, 2020), Singh A, Allen D, Fracassi A, Tumurbaatar B, Natarajan C, Scaduto P, Woltjer R, Kayed R, Limon A, Krishnan B, and Taglialatela G, provides ultimate evidence that preventing/abolishing tau oligomer association with synapses is a key step to maintaining cognitive integrity in human. Synaptic targeting and disruption by small oligomeric aggregates of amyloid beta and tau proteins has been widely recognized as a central event underscoring cognitive decline and clinical manifestation of AD.
This work shows that contrary to fully demented AD patients, synapses of non-demented individuals with AD neuropathology (here referred to as NDAN) are devoid of toxic tau oligomers as determined by immunofluorescence histology and western blot studies on synaptosomes isolated from frozen brain specimens. Most notably, using unique approaches of FASS-LTP on synaptosomes and microtransplantation of human synaptic membranes in Xenopus oocytes coupled to electrophysiology recording, this work provides a rare insight into human synaptic functionality as determined in frozen autopsy brain specimens. The results show that absence of tau oligomers is associated with integrity of FASS-LTP as well as preservation of kainite/GABA current ratio in synapses from NDAN individuals as compared to demented AD patients. Overall, the present paper shows, in actual human brains, the causal relationship between synaptic presence of tau oligomers and disruption of synaptic function by illustrating how the absence of both events underscores the retention of cognitive integrity in the face of abundant AD neuropathology, thus providing further support to the credence of tau oligomers and their targeting of synapses as an effective therapeutic target in AD.
The 2021 Alzheimer Award is proudly sponsored by Alzheimer’s Germ Quest.