RT Journal Article SR Electronic T1 In-vivo tau pathology is associated with synaptic loss and altered synaptic function JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 43 OP 43 VO 62 IS supplement 1 A1 Emma Coomans A1 Deborah Schoonhoven A1 Hayel Tuncel A1 Sander Verfaillie A1 Emma Wolters A1 Ronald Boellaard A1 Rik Ossenkoppele A1 Anouk den Braber A1 Wiep Scheper A1 Patrick Schober A1 Steven Sweeney A1 J Michael Ryan A1 Robert Schuit A1 Albert Windhorst A1 Frederik Barkhof A1 Philip Scheltens A1 Sandeep Golla A1 Arjan Hillebrand A1 Alida Gouw A1 Bart van Berckel YR 2021 UL http://jnm.snmjournals.org/content/62/supplement_1/43.abstract AB 43Objectives: The mechanism of synaptic loss in Alzheimer’s disease is poorly understood and may be associated with tau pathology. In this combined positron emission tomography (PET) and magnetoencephalography (MEG) study, we aimed to investigate spatial associations between regional tau pathology ([18F]flortaucipir PET), synaptic density (synaptic vesicle 2A [11C]UCB-J PET) and synaptic function (MEG) in Alzheimer’s disease. Methods: Seven amyloid-positive Alzheimer’s disease subjects from the Amsterdam Dementia Cohort underwent dynamic 130-minutes [18F]flortaucipir PET, dynamic 60-minutes [11C]UCB-J PET with arterial sampling and 2x5-minutes resting-state MEG measurement. [18F]flortaucipir and [11C]UCB-J specific binding (binding potential, BPND) and MEG spectral measures (relative delta, theta and alpha power, broadband power and peak frequency) were assessed in cortical brain regions of interest. Associations between regional [18F]flortaucipir BPND, [11C]UCB-J PET BPND and MEG spectral measures were assessed using Spearman correlations and generalized estimating equation models. Results: Across subjects, higher regional [18F]flortaucipir uptake was associated with lower [11C]UCB-J uptake. Within subjects, the association between [11C]UCB-J and [18F]flortaucipir depended on within-subject neocortical tau load; negative associations were observed when neocortical tau load was high, gradually changing into opposite patterns with decreasing neocortical tau burden. Both higher [18F]flortaucipir and lower [11C]UCB-J uptake were associated with altered synaptic function, indicative of slowing of oscillatory activity, most pronounced in the occipital lobe. Conclusions: These results indicate that in Alzheimer’s disease tau pathology is closely associated with reduced synaptic density and synaptic dysfunction.