[P3–418]: PARIETAL WHITE MATTER LESIONS IN ALZHEIMER's DISEASE ARE ASSOCIATED WITH CORTICAL NEURODEGENERATIVE PATHOLOGY AND NOT WITH SMALL‐VESSEL DISEASE

• DOI: 10.1016/j.jalz.2017.06.1635
• Publication Date: 2017-10-20T07:32:21Z
• Authors: Kirsty E. McAleese; Lauren Walker; Sophie Graham; Daniel Erskine; Elisa LJ. Moya; Mary Johnson; Sean J. Colloby; Madhurima Dey; John‐Paul Taylor; Alan Thomas; Ian G. McKeith; Charles S. DeCarli; Johannes Attems
• Keywords: Wallerian degeneration; Pathogenesis

Cerebral white matter lesions (WML), as seen histologically, or hyperintensities (WMH) on MRI, are a frequent finding in both demented and non-demented elderly. WML encompass demyelination axonal loss, the pathogenesis is assumed to be small vessel disease (SVD)-related ischemia. However, posterior region, may also occur result of degenerative loss secondary cortical Alzheimer's (AD) pathology, i.e., hyperphosphorylated tau (HPτ) amyloid-beta (Aβ) Wallerian degeneration. It not clear whether pathological molecular signatures AD differ from normal aged, elucidation this paramount for accurate clinical dementia diagnostics. We investigated differences composition parietal using post-mortem human brain tissue aged controls. 55 brains (AD, n = 27; controls, 27) were quantitative assessed severity, demyelination, well measures HPτ, Aβ WM-SVD. Biochemical assessment measured calpain protease (Wallerian degeneration) myelin proteins MAG (ischemia) PLP (axonal atrophy). Our findings support concept AD-pathology, which putative mechanism AD. This new understanding WML/WMH diagnosis patients with cognitive impairment future studies warranted investigate diagnostic accuracy WM changes that