Alzheimer's Disease Organelle Proteome Task (ADOPT)-pilot phase

PROJECT SUMMARY Dysfunctions in organelles such as the mitochondria and lysosomes are increasingly being appreciated to drive various forms of neurodegenerative diseases, such as the Alzheimer's disease and Alzheimer's disease-related dementias (AD/ADRD). However, an integrated organelle proteome consortium in the field of AD/ADRD is lacking. To address this knowledge gap, an interdisciplinary team, consisting of Drs. Biao Wang and Danielle Swaney will form the Alzheimer's Disease Organelle Proteome Task (ADOPT), to quantitatively measure organelle proteome to provide in-depth knowledge of organelle homeostasis and function in the complex brain tissues during the disease progression of AD. This R03 proposal is a pilot phase of ADOPT, in which genetic organelle tagging approach will be utilized to enable rapid purification of lysosome from neurons in wild-type and AD brains from mouse models. A suite of mass spectrometry experiments will quantitatively measure organelle proteome, including protein abundance, post-translational modifications, and protein complexes. Computational modeling will determine lysosomal proteome homeostasis. This systems-to-function approach will shape new scientific paradigms in AD/ADRD research.