Objective: We aimed to investigate whether functional connectivity and white matter integrity is altered in regions exhibiting reduced synaptic density, as measured by [11C]UCB-J-PET,in Dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD).

Background: Synaptic vesicle glycoprotein 2A (SV2A) is a pre-synaptic protein expressed ubiquitously in glutamatergic, GABAergic and neuroendocrine neurons. [11C]UCB-J serves as a novel, selective radioligand for SV2A, thus enables the quantification of synaptic density in vivo.

Method: [11C]UCB-J PET was employed to evaluate synaptic density in 9 PDD and 9 DLB patients compared to 12 age-matched healthy controls. The regions exhibiting decreased [11C]UCB-J volume of distribution, including the precentral gyrus, superior temporal gyrus, supramarginal gyrus, angular gyrus, superior gyrus, striatum, pallidum and substantia nigra for PDD and the frontal, temporal, parietal, insula, cingulate and occipital cortex, alongside the caudate, thalamus and brainstem for DLB were integrated into the rs-fMRI connectivity and DTI analysis.

Results: Compared to healthy controls, DLB patients exhibited reduced connectivity amongst the bilateral insula cortex, the bilateral temporal lobe, the right parietal lobe, and the right anterior cingulate (FDR-correction, P<0.05). PDD exhibited reduced connectivity in the bilateral posterior temporal lobe (FDR-correction,P<0.05). No connectivity alternations were identified in subcortical regions in DLB or PDD groups compared to healthy controls. DLB patients demonstrated decreased FA in the right superior temporal gyrus middle part (P=0.04) and the right insula gyrus (P<0.05). PDD patients did not exhibit FA changes in regions of reduced synaptic density.

Conclusion: Our findings indicate thatregions with synaptic loss also exhibit reduced functional connectivity and microstructural alterations, highlighting that neuronal activity is compromised when synapses are lost. However, a loss of synaptic density does not directly correspond to altered connectivity or microstructural alternations, highlighting the complex relationship between synaptic loss and neuronal activity. *This abstract was also submitted for presentation at the 2019 European Academy of Neurology conference.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/functional-connectivity-and-microstructural-alterations-in-regions-of-synaptic-density-loss-in-dlb-and-pdd/