Parietal white matter lesions in Alzheimer ’s disease are associated with cortical neurodegenerative pathology, but not with small vessel disease

AbstractCerebral white matter lesions (WML) encompass axonal loss and demyelination, and the pathogenesis is assumed to be small vessel disease (SVD)-related ischemia. However, WML may also result from the activation of Wallerian degeneration as a consequence of cortical Alzheimer ’s disease (AD) pathology, i.e. hyperphosphorylated tau (HPτ) and amyloid-beta (Aβ) deposition. WML seen in AD have a posterior predominance compared to non-demented individuals but it is unclear whether the pathological and molecular signatures of WML differ between these two groups. We investi gated differences in the composition and aetiology of parietal WML from AD and non-demented controls. Parietal WML tissue from 55 human post-mortem brains (AD,n = 27; non-demented controls,n = 28) were quantitatively assessed for axonal loss and demyelination, as well as for cortical HPτ and Aβ burden and SVD. Biochemical assessment included Wallerian degeneration protease calpain and the myelin-associated glycoprotein (MAG) to proteolipid protein (PLP) ratio (MAG:PLP) as a measure of hypoperfusion. WML severity was associated with both axonal loss and demyelination in AD, but only with demyelination in controls. Calpain was significantly increased in WML tissue in AD, whereas MAG:PLP was significantly reduced in controls. Calpain levels were associated with increasing amoun ts of cortical AD-pathology but not SVD. We conclude that parietal WML seen in AD differ in their pathological composition a...
Source: Acta Neuropathologica - Category: Neurology Source Type: research