Zane DeMercurio | 2026 I.S. Symposium
狈补尘别:听Zane DeMercurio
罢颈迟濒别:听A Deeper Connection Between Alzheimer鈥檚 and Parkinson鈥檚 Diseases? How GBA Silencing in Drosophila Impacts Tau-Mediated Alzheimer鈥檚 Pathology
惭补箩辞谤:听Neuroscience
础诲惫颈蝉辞谤:听Seth Kelly
The increasing prevalence of neurodegenerative disease, most commonly Alzheimer鈥檚 (AD) and Parkinson鈥檚 Disease (PD), has led many to deeply investigate the basis for these conditions. Research has shown that protein accumulation is often the culprit. Amyloid-尾 and/or tau protein accumulation correlate with AD pathology, while 饾浖-Synuclein is implicated in PD. Recently, a lysosomal protein called glucocerebrosidase, or 鈥楪Case,鈥 has been connected to PD, too. Rather than overexpression, research shows that the reduced expression of this protein, often via mutations to its associated gene (GBA), hastens PD onset and exacerbates PD-associated symptoms. It is theorized that, when GCase is mutated, the lysosomal clearance of 饾浖-Synuclein does not occur effectively. As AD/PD pathogeneses are similar, we infer that this protein may also impact AD in relation to tau clearance. We hypothesized that reduced expression of GCase would worsen AD-associated behavioral symptoms. Using Drosophila as a model organism for neurodegeneration, we tested sleep and locomotor patterns in flies with neuronal tau overexpression and GBA reduction separately, and both conditions together.
Drosophila Activity Monitoring (DAM) revealed that heterozygous GBA genomic deletion unexpectedly induced more consolidated sleep patterns and efficient climbing abilities in Drosophila. In the presence of both neuronal tau overexpression and heterozygous/mild GBA silencing, tau overexpression masked the positive sleep (in females) and locomotor (in males) impacts that mild GBA reduction had on mutated flies. It would be useful in the future to test this hypothesis further with homozygous GBA mutants and to perform quantitative analyses on GCase expression in mutated flies.
Posted in Symposium 2026 on May 1, 2026.
