PMID- 18586353 OWN - NLM STAT- MEDLINE DCOM- 20100608 LR - 20211124 IS - 1558-1497 (Electronic) IS - 0197-4580 (Linking) VI - 31 IP - 4 DP - 2010 Apr TI - Astrocyte phenotype in relation to Alzheimer-type pathology in the ageing brain. PG - 578-90 LID - 10.1016/j.neurobiolaging.2008.05.015 [doi] AB - 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 beta-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. CI - Copyright (c) 2008 Elsevier Inc. All rights reserved. FAU - Simpson, J E AU - Simpson JE AD - Academic Unit of Pathology, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK. FAU - Ince, P G AU - Ince PG FAU - Lace, G AU - Lace G FAU - Forster, G AU - Forster G FAU - Shaw, P J AU - Shaw PJ FAU - Matthews, F AU - Matthews F FAU - Savva, G AU - Savva G FAU - Brayne, C AU - Brayne C FAU - Wharton, S B AU - Wharton SB CN - MRC Cognitive Function and Ageing Neuropathology Study Group LA - eng GR - G0300126/MRC_/Medical Research Council/United Kingdom GR - G9901400/MRC_/Medical Research Council/United Kingdom GR - MC_U105292687/MRC_/Medical Research Council/United Kingdom PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20080630 PL - United States TA - Neurobiol Aging JT - Neurobiology of aging JID - 8100437 RN - 0 (Amyloid beta-Peptides) RN - 0 (Biomarkers) RN - 0 (Excitatory Amino Acid Transporter 1) RN - 0 (Excitatory Amino Acid Transporter 2) RN - 0 (Glial Fibrillary Acidic Protein) RN - 0 (Nerve Growth Factors) RN - 0 (Nerve Tissue Proteins) RN - 0 (S100 Calcium Binding Protein beta Subunit) RN - 0 (S100 Proteins) RN - 0 (S100B protein, human) RN - 0 (tau Proteins) SB - IM MH - Aged MH - Aged, 80 and over MH - Alzheimer Disease/metabolism/*pathology/physiopathology MH - Amyloid beta-Peptides/analysis/metabolism MH - Astrocytes/metabolism/*pathology MH - Biomarkers/analysis/metabolism MH - Brain/metabolism/*pathology/physiopathology MH - Cohort Studies MH - Excitatory Amino Acid Transporter 1/analysis/metabolism MH - Excitatory Amino Acid Transporter 2/analysis/metabolism MH - Female MH - Glial Fibrillary Acidic Protein/analysis/metabolism MH - Gliosis/metabolism/*pathology/physiopathology MH - Humans MH - Immunohistochemistry MH - Longitudinal Studies MH - Male MH - Nerve Growth Factors/analysis/metabolism MH - Nerve Tissue Proteins/analysis/metabolism MH - Phenotype MH - Plaque, Amyloid/metabolism/pathology MH - Predictive Value of Tests MH - Prospective Studies MH - S100 Calcium Binding Protein beta Subunit MH - S100 Proteins/analysis/metabolism MH - Severity of Illness Index MH - tau Proteins/analysis/metabolism EDAT- 2008/07/01 09:00 MHDA- 2010/06/09 06:00 CRDT- 2008/07/01 09:00 PHST- 2007/12/07 00:00 [received] PHST- 2008/02/29 00:00 [revised] PHST- 2008/05/18 00:00 [accepted] PHST- 2008/07/01 09:00 [pubmed] PHST- 2010/06/09 06:00 [medline] PHST- 2008/07/01 09:00 [entrez] AID - S0197-4580(08)00170-X [pii] AID - 10.1016/j.neurobiolaging.2008.05.015 [doi] PST - ppublish SO - Neurobiol Aging. 2010 Apr;31(4):578-90. doi: 10.1016/j.neurobiolaging.2008.05.015. Epub 2008 Jun 30.