A postmortem examination of brain tissue from 20 people with dementia with Lewy bodies (DLB) and 20 people without the disease found that the density of Lewy bodies, the misfolded alpha-synuclein protein clumps that define the disease, was not associated with the loss of neurons or synaptic proteins, according to a study published in Neuropathology and Applied Neurobiology. The finding held even in the cingulate gyrus, one of two brain regions studied where Lewy body burden was heaviest.
Researchers at Newcastle University examined tissue from the cingulate gyrus and inferior temporal gyrus, two regions known to accumulate Lewy pathology early in the disease. Using a neuronal marker, they found total neuron density did not differ between the DLB and control groups in either region. A specific subtype of neuron, parvalbumin-expressing interneurons, was significantly lower in DLB tissue from the cingulate gyrus but not from the temporal region. Synaptic marker proteins, measured separately by immunoblot on frozen tissue, were only modestly reduced in DLB tissue compared with controls. Lewy body density varied widely from case to case and, notably, tracked with the amount of amyloid-beta, the plaque protein associated with Alzheimer's disease, present in the same tissue.
The results run against a working assumption in the field: that Lewy bodies themselves, or the process that forms them, directly kill neurons and break down synaptic connections, producing the cognitive and movement symptoms of DLB. This postmortem, cross-sectional sample of 40 brains cannot establish what happened over the course of anyone's illness, and the study's authors were explicit that their findings challenge, rather than settle, the question of how alpha-synuclein contributes to disease.