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The aetiology of frontal white matter lesions in Alzheimer’s disease are associated with both neurodegenerative and ischemic mechanisms
Author(s) -
McAleese Kirsty E.,
Miah Mohi,
Graham Sophie,
Baker Georgie,
Walker Lauren,
DeCarli Charles,
Koss David,
Attems Johannes
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.043253
Subject(s) - hyperintensity , wallerian degeneration , leukoaraiosis , white matter , medicine , pathology , myelin , pittsburgh compound b , pathogenesis , alzheimer's disease , disease , magnetic resonance imaging , dementia , central nervous system , radiology
Background We have previously shown that the pathogenesis of parietal white matter lesions (WML) seen in Alzheimer’s disease (AD) can be associated with degenerative loss as a result of Wallerian degeneration activated by hyperphosphorylated tau (HPτ) [1]. In a subset of these cases, we investigated the the pathological composition and aetiology of WML from the frontal region. Method Frontal WML from 40 post‐mortem brains (AD, n=19; controls, n=21) were quantitative assessed for WML severity, axonal loss and demyelination, as well cortical measures of HPτ, amyloid‐beta (Aβ) and WM‐small vessel disease (SVD) score. Biochemical assessment included the Wallerian degeneration‐associated protease calpain and the ratio of myelin‐associated glycoprotein (MAG) and proteolipid protein (PLP) as a measure of hypoperfusion. Result No significant difference was revealed in WML severity between controls and AD. WML severity was associated with axonal and myelin loss in AD (both P<0.02), but only myelin loss in controls (P<0.0001). WML severity correlated with WM‐SVD score in both controls (P<0.0001) and AD (P <0.05); no association between WML severity and HPτ was revealed in the AD group. Calpain was increased in AD but this was not significant, and calpain correlated with Aβ (P<0.05). No significant difference was seen in MAG:PLP between AD and controls. Conclusion Frontal WML in AD are likely influenced by both ischemic and degenerative mechanisms in contrast to the posterior WM that has a prominent degenerative influence. This study highlights important regional differences in the pathogenesis of WML that may be diagnostically relevant. (1) McAleese et al (2017) DOI 10.1007/s00401‐017‐1738‐2