Cerebral white matter lesions (WML), as seen histologically, or white matter hyperintensities (WMH) as seen on MRI, are a frequent finding in both demented and non-demented elderly. WML encompass demyelination and axonal loss, and thought to result from small vessel disease (SVD)-related ischemia. However, WML may also occur as the result of degenerative axonal loss, secondary to cortical Alzheimer’s disease (AD) pathology (hyperphosphorylated tau (HPτ) and amyloid-beta), as a result of Wallerian degeneration. It is not clear whether the pathological and molecular signatures in WML seen in AD differ from those in ‘normal aged' individuals.
Using a combination of post-mortem MRI, extensive quantitative neuropathological assessment and biochemical analysis, our data has revealed pathological and molecular differences in WML between AD and normal ageing. Notably, WML are associated with cortical AD-pathology not SVD. Understanding the pathogenesis of WML is therefore paramount for the accuracy of clinical dementia diagnostics and future studies will investigate the diagnostic accuracy of specific AD white matter changes.
Using a combination of post-mortem MRI, extensive quantitative neuropathological assessment and biochemical analysis of human white matter tissue, which was generously donated to the Newcastle Brain and Tissue Resource. Our data has revealed pathological and molecular differences in WML between AD and normal ageing that are associated with increasing amounts of cortical AD-pathology not SVD. Understanding of the pathogenesis of WML/WMH in AD is paramount for the accurate diagnosis of patients with cognitive impairment, and future studies are warranted to investigate diagnostic accuracy of specific AD white matter changes.
This project is lead by Dr Kirsty E. McAleese and funded by the Alzheimer’s Society.
Publication
McAleese KE, Firbank M, Dey M, Colloby SJ, Walker L, Johnson M, Beverley JR, Taylor JP, Thomas AJ, O'Brien JT, Attems J (2015) Cortical tau load is associated with white matter hyperintensities. Acta Neuropathol Commun 3:60.