Astrocyte phenotype in relation to Alzheimer-type pathology in the ageing brain

Simpson, J.E.; Ince, P.G.; Lace, G.; Forster, G.; Shaw, P.J.; Matthews, F.; Savva, G.; Brayne, C.; Wharton, S.B.; on behalf of the MRC Cognitive Function and Ageing Neuropathology Study Group,

doi:10.1016/j.neurobiolaging.2008.05.015

« Previous Next »Neurobiology of Aging
Volume 31, Issue 4 , Pages 578-590, April 2010

Astrocyte phenotype in relation to Alzheimer-type pathology in the ageing brain

J.E. Simpson
- Academic Unit of Pathology, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK
P.G. Ince
- Academic Unit of Pathology, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK
G. Lace
- Academic Unit of Pathology, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK
G. Forster
- Academic Unit of Pathology, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK
P.J. Shaw
- Academic Unit of Neurology, University of Sheffield Medical School, Sheffield S10 2RX, UK
F. Matthews
- MRC Biostatistics Unit, Institute of Public Health, University of Cambridge, Cambridge, UK
G. Savva
- MRC Biostatistics Unit, Institute of Public Health, University of Cambridge, Cambridge, UK
C. Brayne
- Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, Cambridge, UK
S.B. Wharton
- Academic Unit of Pathology, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK
- Corresponding author. Tel.: +44 114 226 1342; fax: +44 114 226 1464.
on behalf of the MRC Cognitive Function and Ageing Neuropathology Study Group

Received 7 December 2007; received in revised form 29 February 2008; accepted 18 May 2008. published online 01 July 2008.

Abstract

Astrocyte pathology occurs in association with Alzheimer's disease (AD) and in brain ageing, but is poorly characterised. We sought to define the detailed cellular pathology of astrocytes, the extent of population variation and the relationship to Alzheimer-type changes in a population-based cohort. Three staining patterns were associated with GFAP and excitatory amino acid transporter 2 (EAAT2): minimal, moderate or extensive immunoreactivity. GFAP and EAAT2 expression were inversely related (p=0.015), with trends to increased expression of GFAP (p=0.019) and decreased expression of EAAT2 (p=ns) with increasing Braak stage. GFAP and EAAT2 correlated incompletely with β-amyloid and tau immunoreactivity. However, gliosis increased with increasing burden of neuritic (p=0.011), but not diffuse (p=ns), plaques. Double-staining revealed distinct subsets of astrocytes; GFAP⁺EAAT⁻, GFAP⁻EAAT⁺, or GFAP⁺EAAT⁺. In contrast to the variation in GFAP and EAAT2, levels of EAAT1 and S100B showed consistent staining patterns. Alzheimer-type pathology only partially explains the variation in gliosis and astrocyte functional markers, suggesting that other factors contribute to the population variance in astrocyte pathology.