ABSTRACT Aims The misfolding and accumulation of the protein α ‐synuclein ( α Syn) into cytoplasmic inclusions termed Lewy bodies (LBs) and Lewy neurites is the defining neuropathological feature of LB diseases, such as Parkinson's disease (PD) and dementia with Lewy bodies (DLB). The loss of neurons and/or synapses has been postulated to underlie the clinical syndrome of DLB. The present study sought to elucidate the relationship between LB burden and neuronal and synaptic loss in DLB. Methods Post‐mortem brain tissue from the cingulate gyrus and inferior temporal gyrus, two regions vulnerable to LB pathology, was obtained from DLB ( N = 20) and control cases ( N = 20). Formalin‐fixed paraffin‐embedded tissue was stained to quantify LB, Alzheimer‐type pathology and a neuronal marker. Frozen tissue from the contralateral hemisphere was processed for immunoblotting to compare the abundance of synaptic markers across cases. Results Across both regions, no evidence of reduced total neuronal density was observed, but a modest reduction in parvalbumin interneurons was observed in the cingulate gyrus, and there were only modest reductions in some synaptic markers in DLB. LB burden was markedly variable across DLB cases but was not associated with any synaptic marker abundance or neuronal density. Conclusions Taken together, these findings do not support an association between LB density and neuronal or synaptic loss in DLB, even in regions with particularly high burdens of LBs, such as the cingulate gyrus. These findings suggest that the link between α Syn proteinopathy and disease requires further investigation.
Hawksworth et al. (2026) studied this question.