Title: Synaptic density is correlated with Aβ plaques and neurofibrillary tau tangles across the clinical and biologic Alzheimer’s disease continuum
Citation: Alexandra H DiFilippo, MS1, Max McLachlan, BS1, Andrew K McVea, MS1, Brecca Bettcher,BS1, Erin M. Jonaitis, PhD2, Gilda E. Ennis, PhD2, Mary-Elizabeth Pasquesi, BS2, Nancy J Davenport2, Yer Thor, BS2, Ethan Grover, BS2, Sarah Hudson, BS2, Todd E Barnhart, PhD2, Jonathan W Engle, PhD2, Tobey J Betthauser, PhD2, Sterling C Johnson, PhD2, Barbara B Bendlin, PhD2 and Bradley T. Christian, PhD1,2 , 1 University of Wisconsin-Madison, Waisman Center, Madison, WI, US 2 University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, US. (2023). Presented at the Alzheimer’s Imaging Consortium at the Alzheimer’s Association International Conference in Amsterdam, July 2023
Abstract: Background – The extent to which amyloid-β burden and neurofibrillary tau tangle burden are associated with synaptic degeneration in vivo is not well known. PET imaging was used to examine the cross-sectional relationship between neurofibrillary tau tangle burden and amyloid-β plaque burden with synaptic density among individuals who spanned the clinical and biologic Alzheimer’s disease continuum. Method – Participants were recruited from the Wisconsin Alzheimer’s Disease Research Center and the Wisconsin Registry for Alzheimer’s Prevention study. N=64 participants were included in the analysis based on completed cognitive testing, structural MR and PET imaging using [11C]PiB DVR for amyloid burden, [18F]MK-6240 SUVR for regional neurofibrillary tau burden, and [11C]UCB-J DVR for regional synaptic density burden analysis. Amyloid burden was indexed as a global [11C]PiB DVR representing the mean of brain regions that typically accumulate amyloid. UCB-J DVR and MK-6240 SUVR regions of interest were selected based on the histopathological staging of tau pathology in Alzheimer’s disease with a focus on regions of tau pathology described by earlier and later Braak stages. The first composite region of interest (ROI1) comprised the hippocampus and entorhinal cortex, and the second (ROI2) comprised the amygdala, fusiform, lingual gyrus, and the inferior temporal gyrus. Linear correlations (Pearson’s r) tested the relationship between UCB-J DVR and PiB DVR, as well as UCB-J DVR and MK-6240 SUVR. Results – Global [11C]PiB DVR showed a moderate negative relationship with UCB-J DVR in ROI1 (r = -0.42, p = 0.0006) and a weak relationship with UCB-J DVR in ROI2 (r = -0.33, p = 009). [18F]MK-6240 SUVR and UCB-J DVR were negatively correlated in ROI1 (r = -0.44, p = 0.0003) and in ROI2 (r = -0.42, p = 0.005). Conclusion – Both amyloid burden and tau pathology were associated with lower synaptic density. Tau and synaptic density appeared to show moderate correlations among brain regions involved in both earlier and more advanced tau pathology, whereas amyloid burden appeared to be more strongly related to synaptic density in brain regions where more advanced disease is typically observed.
About the Lab: Our research focuses on developing and translating novel PET methods for the study of neurodevelopment and neuropsychiatric illness. This involves using PET methodologies to investigate neurochemical changes in the brain and studying novel radioligands to characterize neurotransmitter-protein interactions and how they are influenced by development, genes, environment and drugs. These imaging methods are being applied to investigate the etiologies and mechanisms in diseases such as Down syndrome, affective disorders, schizophrenia, Alzheimer’s disease and Tourette syndrome.
Investigator: Brad Christian, PhD