Speaker: Dr. Steffany Bennett Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Canada The glycerophospholipidome in Alzheimer Disease: The missing link between amyloid beta and tau? The aberrant processing of the amyloid precursor protein to different assemblies of amyloid β (Aβ) peptides ranging between 37 and 42 amino acids is an early and necessary prerequisite for the development of Alzheimer Disease (AD). The "amyloid cascade hypothesis" defines generation of these smaller, toxic Aβ fragments, specifically soluble Aβ42 oligomers, as the root cause of AD. The severity of AD progression, however, is highly correlated with the rate of abnormal tau processing, the other signature AD pathology. Underlying molecular mechanisms linking Aβ42 biogenesis to the pathogenic processing of normally soluble tau proteins into hyperphosphorylated oligomers, paired helical filaments, and finally neurofibrillary tangles remain elusive. Exposure to choline-containing glycerophospholipids can elicit conformational changes in tau exposing epitopes that become phosphorylated in AD in situ. Here, using an unbiased lipidomics approach, we profile changes in the glycerophospholipidome in AD with mechanistic evidence that Aβ42 disruption of akylacylglycerophosphocholine metabolism signals tau hyperphosphorylation in AD.