Frontal white matter lesions in Alzheimer ’s disease are associated with both small vessel disease and AD-associated cortical pathology

AbstractCerebral white matter lesions (WML) encompass axonal loss and demyelination and are assumed to be associated with small vessel disease (SVD)-related ischaemia. However, our previous study in the parietal lobe white matter revealed that WML in Alzheimer ’s disease (AD) are linked with degenerative axonal loss secondary to the deposition of cortical AD pathology. Furthermore, neuroimaging data suggest that pathomechanisms for the development of WML differ between anterior and posterior lobes with AD-associated degenerative mechanism driving poster ior white matter disruption, and both AD-associated degenerative and vascular mechanisms contributed to anterior matter disruption. In this pilot study, we used humanpost-mortem brain tissue to investigate the composition and aetiology of frontal WML from AD and non-demented controls to determine if frontal WML are SVD-associated and to reveal any regional differences in the pathogenesis of WML. Frontal WML tissue sections  from 40 humanpost-mortem brains (AD,n  = 19; controls,n  = 21) were quantitatively assessed for demyelination, axonal loss, cortical hyperphosphorylated tau (HP τ) and amyloid-beta (Aβ) burden, and arteriolosclerosis as a measure of SVD. Biochemical assessment included Wallerian degeneration-associated protease calpain and the myelin-associated glycoprotein to proteolipid protein ratio as a measure ofante-mortem ischaemia. Arteriolosclerosis severity was found to be associated with and a signif...
Source: Acta Neuropathologica - Category: Neurology Source Type: research