Dissociation of functional status from accrual of CML and RAGE in the aged mouse brain

The objectives Of this Study Were: (i) to identify regions of the aged Mouse brain in which advanced glycation end-products (AGEs) were increased, and (ii) assess the functional significance of AGEs by determining the extent to which they could predict age-related brain dysfunction. Densitometric analyses of immunoblots for N epsilon-(carboxymethyl)lysine (CML), a predominant AGE, and receptor for AGE (RAGE), were performed in different brain regions of mice aged 8 or 25 months. The 25-month-old mice were tested for ability to perform oil tests of cognitive and psychomotor function prior to assessment of CML or RACE, to determine if immunostaining results Could predict functional impairment among the older mice. The amounts of CML increased with age in cortex, hippocampus, striatum, and midbrain, but Were unchanged in the brainstem and cerebellum. Increases in RAGE were evident in all brain regions but the hippocampus, and were not linked to increased amounts of CML Different statistical approaches each failed to reveal any strong association between the degree of age-related functional impairment among individual mice and amounts of CML or RACE in ally particular region of the brain. The findings from this study suggest that accrual of CML and expression of RACE in different brain regions are time-related phenomena that do not account for individual differences in brain aging or cognitive decline. (c) 2008 Elsevier Inc. All rights reserved.