Neurodegeneration: Prion-like Behavior of Misfolded Proteins in the Syntactic Network (P3.184)

Objective: To determine whether tau deposition in non-fluent primary progressive aphasia (nfPPA) follows a network pattern. Background: Animal studies and the brain atrophy pattern of neurodegenerative dementias suggest that misfolded proteins may propagate in a manner similar to infectious prions, spreading through brain networks. However, this propagation has not been demonstrated in vivo in humans. Design/Methods: Eight nfPPA patients, all PET amyloid-negative, and eight healthy controls had 18 F-AV-1451 PET. The SUV ratio over the cerebellar gray matter was calculated for t = 80–100 min. The two groups were compared using SPM. MRI tractography was performed in the nfPPA group. Additionally, in a different group of 35 healthy subjects with similar age as the nfPPA patients, we determined normal network functional connectivity with BOLD MRI using the voxel most often activated in syntactic tasks as seed. Results: nfPPA patients had impaired language production and increased 18 F-AV-1451 uptake in two major clusters (p Conclusions: Increased 18 F-AV-14510 signal in nfPPA most likely reflects binding to abnormal tau. Binding was greatest in Broca’s area, where degeneration begins in nfPPA, and, to a lesser extent, in the posterior node of the syntactic network. The arcuate fasciculus was thinned in the left hemisphere suggesting that it is the pathway traveled by misfolded proteins associated with neuronal and axonal degeneration. Our findings provide in vivo evidence that, in neurodegenerative dementia, misfolded proteins propagate in a prion-like manner. Study Supported by: This study was supported by the Chao, Graham, Harrison and Nantz Funds of the Houston Methodist Foundation and by AVID Radio pharmaceuticals. Disclosure: Dr. Pascual has nothing to disclose. Dr. Funk has nothing to disclose. Dr. Zanotti Fregonara has nothing to disclose. Dr. Rockers has nothing to disclose. Dr. Pal has nothing to disclose. Dr. Yu has nothing to disclose. Dr. Karmonik has nothing to disclose. Dr. Spann has nothing to disclose. Dr Roman has nothing to disclose. Dr. Schulz has nothing to disclose. Dr. Masdeu has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with General Electric Health.