Brain regions age unequally in Lewy body dementia
Not all parts of the brain decline at the same rate in Lewy body dementia. More complex, highly connected regions appear more vulnerable than simpler ones, and new research helps explain why.
The researchers compared MRI brain scans from 89 patients with dementia with Lewy bodies against 89 matched healthy controls. They measured which cortical regions thinned most and linked those patterns to gene expression data from postmortem human brains.
What are Lewy bodies?
Dementia with Lewy bodies is caused by the accumulation of a misfolded protein called alpha-synuclein in the brain. As it spreads through the central nervous system, it triggers cell damage and death in important neuron populations. The disease shares features with both Parkinson’s disease and Alzheimer’s disease.
The study found that brain regions showing the most shrinkage were, in healthy brains, defined by higher activity of genes involved in mitochondria (the cell’s energy-producing organelles) and in signalling between neurons. These regions appear more fragile, possibly because of their higher energy demands and greater exposure to misfolded protein.
Selective vulnerability, not random degeneration
Beyond the overlap with known Parkinson’s and Alzheimer’s gene pathways, the researchers also identified 90 genes unique to Lewy body dementia, enriched for a specific inhibitory signalling network known as the GABAergic system. The spatial pattern of cortical thinning also followed the brain’s structural connectivity, consistent with the idea that misfolded alpha-synuclein spreads along existing neural pathways.
The finding that more metabolically active and interconnected brain regions are hit hardest is notable from a longevity perspective. It raises questions about whether protecting mitochondrial function might slow this pattern of damage. The study does not answer that question directly, but it does reframe Lewy body dementia as a disease governed by specific molecular and network vulnerabilities, not an indiscriminate process. That distinction matters for early detection and targeted treatment research.
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Search terms: alpha-synuclein cortical thinning, mitochondrial vulnerability neurodegeneration, GABAergic signalling Lewy body dementia