ASYMMETRIC EXPRESSION PATTERNS OF BRAIN TRANSTHYRETIN IN NORMAL MICE AND A TRANSGENIC MOUSE MODEL OF ALZHEIMER'S DISEASE

Brain asymmetry is linked with several neurological diseases, and transthyretin (TTR) is a protein sequestering beta-amyloid (A beta) and helping to prevent the Alzheimer's disease (AD). We show, by real time reverse transcription-polymerase chain reaction (RT-PCR), in situ hybridization and Western blotting, that TTR exhibits a pattern of adult male-specific, leftward distribution in the mouse brain. This asymmetry appeared to be mainly due to the asymmetric distribution of the choroid plexus cells in the ventricles. Unlike the normal mice, however, the hemispheric levels of TTR transcripts of 2- and 6-month-old Tg2576 mice, a transgenic AD mouse model overexpressing A beta, were symmetric in both sexes. Furthermore, at the age of 10 months when the pathological AD-like features had developed, the level of TTR transcripts in the left hemisphere of the male Tg2576 became significantly lower than the right one. This lowering of TTR transcript is accompanied with a higher A beta level in the left hemisphere of the 10-month Tg2576 males. Finally, for both genders, the TTR transcript levels in the two hemispheres of aged Tg2576 mice were lower than either the adult Tg2576 or the aged nontransgenic controls. Based on the above, we suggest scenarios to correlate the changes in the levels and hemispheric patterns of TTR expression to the pathogenesis of AD. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.