P1–030: Analysis of gene expression in brains of tg–APP–ArcSwe mice, a model for Alzheimer's disease

sor protein (APP)-transgenic mice and the involvement of apolipoprotein E (apoE) in this process. Methods: Immunohistochemistry was used to demonstrate the presence of A and apoE within the perivascular space of 25-month-old wild-type and amyloid precursor protein (APP)-transgenic mice harboring the Swedish double mutation. The congo red method was used to test whether A -positive material represents amyloid material. Results: Only small amounts of A were detected immunohistochemically in the perivascular space of wild-type mice. Cerebrovascular and parenchymal A -deposits were absent in wild-type mice. On the other hand, in APP-transgenic mice large amounts of A were found in the perivascular drainage channels accompanied with cerebrovascular and parenchymal A -deposition. The amount of apoE positive material within the perivascular channels did not vary between wild-type and APP-transgenic mice. Almost 100% of the area that represents the perivascular space was stained with an antibody directed against apoE. Here, A co-localized with apoE indicating an involvement of apoE in the perivascular clearance of A . Fibrillar congophilic amyloid was not seen in the perivascular space of wild-type mice but in that of APP-transgenic animals. Conclusions: Our results strongly support the notion that A is drained along perivascular channels and that apoE is presumably involved in this clearance mechanism. Overloading such a clearance mechanism in APP-transgenic mice apparently results in insufficient A -clearance, increased A -levels in the brain and the perivascular drainage channels, and finally in A -deposition. Thus, our results strengthen the hypothesis that an alteration of perivascular drainage supports A -deposition and the development of AD. This study was supported by DFG-grant: TH624/4-2.