Correlation Of Microglial Activation With White Matter Changes In Dementia With Lewy Bodies

Nicastro, N.; Mak, E.; Williams, G. B.; Surendranathan, A.; Bevan-Jones, W. R.; Passamonti, L.; Vazquez-Rodriguez, P.; Su, L.; Arnold, R.; Aigbirhio, F. I.; Rowe, J. B.; O'Brien, J. T.

doi:10.1101/599241

bioRxiv · 10.1101/599241

Correlation Of Microglial Activation With White Matter Changes In Dementia With Lewy Bodies

Nicastro, N.·Mak, E.·Williams, G. B.·Surendranathan, A.·Bevan-Jones, W. R.·Passamonti, L.·Vazquez-Rodriguez, P.·Su, L.·Arnold, R.·Aigbirhio, F. I.·Rowe, J. B.·O'Brien, J. T.

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Abstract

Dementia with Lewy bodies (DLB) is the second-leading degenerative dementia after Alzheimers disase. Neuropathologically, it is characterized by alpha-synuclein protein deposition with variable degree of concurrent Alzheimer pathology. Neuroinflammation is increasingly recognized as a significant contributor of degeneration.\n\nObjectiveto examine the relationship between microglial activation as measured with [11C]-PK11195 brain PET and MR diffusion tensor imaging (DTI) in DLB.\n\nMethodsnineteen clinically probable DLB and 20 similarly aged controls underwent structural MRI with T1-weighted and 3T DTI sequences. Eighteen DLB subjects also underwent [11C]-PK11195 PET imaging. Tract-Based Spatial Statistics (TBSS) were performed to compare DTI parameters in DLB relative to controls and identify associations of [11C]-PK11195 binding with white matter integrity.\n\nResultsTBSS showed widespread changes in all DTI parameters in the DLB group compared to controls (Threshold Free Cluster Enhancement (TFCE) p < 0.05). [11C]-PK11195 binding in parietal cortices also correlated with widespread lower mean and radial diffusivity (TFCE p < 0.05).\n\nConclusionOur study demonstrates that higher PK11195 binding is associated with a relative preservation of white matter, positioning neuroinflammation as a potential early marker in the DLB pathogenic cascade.

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Nicastro, N., Mak, E., Williams, G. B., Surendranathan, A., Bevan-Jones, W. R., Passamonti, L., Vazquez-Rodriguez, P., Su, L., Arnold, R., Aigbirhio, F. I., Rowe, J. B., O'Brien, J. T.. 2019-04-09. Correlation Of Microglial Activation With White Matter Changes In Dementia With Lewy Bodies. https://doi.org/10.1101/599241

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