Pick's disease is a subset of fronto-temporal dementia characterised by severe 
atrophy of the temporal and frontal lobes due to marked neuronal loss 
accompanied by astrocytic gliosis enriched in glial acidic protein. The 
remaining neurones have intracytoplasmic inclusions composed of 
hyperphosphorylated tau, called Pick bodies, in addition to hyperphosphorylated 
tau in astrocytes and oligodendrocytes. Gel electrophoresis and western blotting 
using markers of glycoxidation (advanced glycation end products, 
N-carboxyethyl-lysine and N-carboxymethyl-lysine: AGE, CEL, CML, respectively) 
and lipoxidation (4-hydroxy-2-nonenal: HNE, and malondialdehyde-lysine: MDAL) 
were used in the frontal and occipital cortex in three Pick's disease cases and 
three age-matched controls. In Pick's disease, increased AGE, CML, CEL, HNE and 
MDAL bands of about 50 kDa were observed in the frontal cortex (but not in the 
occipital cortex) in association with increased density of glial acidic protein 
bands. Bi-dimensional gel electrophoresis and western blotting also disclosed 
increased amounts and numbers of glial acidic protein isoforms in the frontal 
cortex in Pick's disease. Moreover, redox proteomics showed glycoxidation, as 
revealed with anti-CEL antibodies and lipoxidation using anti-HNE antibodies, of 
at least three glial acidic protein isoforms. The present results demonstrate 
that glial acidic protein is a target of oxidative damage in the frontal cortex 
in Pick's disease.