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.