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White matter lesions in an unselected cohort of the elderly: Astrocytic, microglial and oligodendrocyte precursor cell responses

Lookup NU author(s): Professor John O'Brien, Dr Robert Barber, Professor Raj Kalaria, Professor Carol Brayne, Professor Pamela Shaw


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Hyperintense lesions are frequently identified in T2-weighted magnetic resonance images (MRI) in the ageing brain. The pathological correlate and pathogenesis of white matter lesions (WML) remain unclear, and it is uncertain whether pathology and pathogenesis differ in periventricular lesions (PVL) compared with deep subcortical lesions (DSCL). Therefore we characterized astrocytic, microglial and oligodendrocyte responses in PVL and DSCL and compared them with control white matter using immunohistochemistry. Both PVL and DSCL were associated with severe myelin loss and increased microglia (P = 0.069 and P < 0.001), compared with nonlesional aged brain. Clasmatodendritic astroglia, immunoreactive for the serum protein fibrinogen, were present in 67% of PVL examined and 42% of DSCL. Compared with control and DSCL cases, more MAP-2 +13 positive remyelinating oligodendrocytes (P = 0.003 and P = 0.035) and platelet-derived growth factor α receptor positive reactive astrocytes (P < 0.001) were present in the perilesional white matter of PVL. In addition to a role for hypoperfusion, our data suggest that dysfunction of the blood-brain barrier may also contribute to the pathogenesis of a proportion of cerebral WML associated with ageing, and that attempts at remyelination are only associated with PVL and not DSCL. © 2007 Blackwell Publishing Ltd.

Publication metadata

Author(s): Simpson JE, Fernando MS, Clark L, Ince PG, Matthews F, Forster G, O'Brien JT, Barber R, Kalaria RN, Brayne C, Shaw PJ, Lewis CE, Wharton SB

Publication type: Article

Publication status: Published

Journal: Neuropathology and Applied Neurobiology

Year: 2007

Volume: 33

Issue: 4

Pages: 410-419

ISSN (print): 0305-1846

ISSN (electronic): 1365-2990

Publisher: Wiley-Blackwell Publishing Ltd.


DOI: 10.1111/j.1365-2990.2007.00828.x


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G0400074Medical Research Council
G0502157Medical Research Council
G9901400Medical Research Council
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G0500247Medical Research Council
MC_U105292687Medical Research Council