BetaAPP and furin mRNA concentrates in immature senile plaques in the brain of Alzheimer patients

This study examined the possibility that in Alzheimer disease (AD) beta-amyloid precursor protein (betaAPP) mRNA is delivered to senile plaques (SPs) via dendritic processes. BetaAPP mRNA was detected in SPs by in situ hybridization, using a 1.4-kb cRNA in which both [35S]-UTP and [35S]-CTP were incorporated together. The betaAPP mRNA was compared with that of furin, a proteolytic enzyme putatively involved in betaAPP processing, and its orthologue proprotein convertase PCI served as a control. Human presenile AD cases with mostly immature SPs and AD cases generally with mature SPs were analyzed. To decrypt SPs after hybridization, brain sections were stained with thioflavin S. To establish relationships between the density of dystrophic fibers, the degree of plaque maturation, and the concentration of mRNA in SPs, the plaque maturity markers Abeta(1-42) and Abeta(1-40) peptides were co-localized with neurofilament protein 200 and compared with microtubule-associated protein 2 (MAP 2). The results suggest that immature, Abeta(1-42)- and dystrophic dendrite-containing SPs (but not mature SPs containing Abeta(1-40) and missing dystrophic dendrites) are capable of concentrating specific mRNAs. Dystrophic dendrites may thus serve as a route for the transport of specific mRNAs from the cell bodies to SPs.