Skip to main content

21.06.2017 | Original Paper | Ausgabe 3/2017 Open Access

Acta Neuropathologica 3/2017

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

Acta Neuropathologica > Ausgabe 3/2017
Kirsty E. McAleese, Lauren Walker, Sophie Graham, Elisa L. J. Moya, Mary Johnson, Daniel Erskine, Sean J. Colloby, Madhurima Dey, Carmen Martin-Ruiz, John-Paul Taylor, Alan J. Thomas, Ian G. McKeith, Charles De Carli, Johannes Attems
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1007/​s00401-017-1738-2) contains supplementary material, which is available to authorized users.


Cerebral 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 investigated 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 amounts of cortical AD-pathology but not SVD. We conclude that parietal WML seen in AD differ in their pathological composition and aetiology compared to WML seen in aged controls: WML seen in AD may be associated with Wallerian degeneration that is triggered by cortical AD-pathology, whereas WML in aged controls are due to ischaemia. Hence, parietal WML as seen on MRI should not invariably be interpreted as a surrogate biomarker for SVD as they may be indicative of cortical AD-pathology, and therefore, AD should also be considered as the main underlying cause for cognitive impairment in cases with parietal WML.

Unsere Produktempfehlungen

e.Med Interdisziplinär


Mit e.Med Interdisziplinär erhalten Sie Zugang zu allen CME-Fortbildungen und Fachzeitschriften auf Zusätzlich können Sie eine Zeitschrift Ihrer Wahl in gedruckter Form beziehen – ohne Aufpreis.

e.Med Neurologie & Psychiatrie


Mit e.Med Neurologie & Psychiatrie erhalten Sie Zugang zu CME-Fortbildungen der Fachgebiete, den Premium-Inhalten der dazugehörigen Fachzeitschriften, inklusive einer gedruckten Zeitschrift Ihrer Wahl.

e.Med Neurologie


Mit e.Med Neurologie erhalten Sie Zugang zu CME-Fortbildungen des Fachgebietes, den Premium-Inhalten der neurologischen Fachzeitschriften, inklusive einer gedruckten Neurologie-Zeitschrift Ihrer Wahl.

Supplementary material 1 (DOCX 88 kb)
Supplementary material 2 (DOCX 101 kb)
Über diesen Artikel

Weitere Artikel der Ausgabe 3/2017

Acta Neuropathologica 3/2017 Zur Ausgabe

Neu im Fachgebiet Pathologie

01.11.2018 | Schwerpunkt: Immunpathologie | Ausgabe 6/2018

Der prädiktive Wert der PD-L1-Diagnostik

22.10.2018 | Schwerpunkt: Immunpathologie | Ausgabe 6/2018

Digitale Pathologie in der Immunonkologie – Aktuelle Chancen und Herausforderungen

Überblick zur Analyse von Immunzellinfiltraten mittels Whole Slide Imaging

22.10.2018 | Schwerpunkt: Immunpathologie | Ausgabe 6/2018

Prognostische Bedeutung von Immunzellinfiltraten in der Tumorpathologie