The breakdown of neurovascular systems may play a crucial role in the pathogenesis of Alzheimer’s
disease. However whether this breakdown initiates a degenerative mechanism or is the consequence of
some other deleterious process remains unknown. We examined hippocampal pathology in double
transgenic mice overexpressing a human mutant gene encoding the amyloid precursor protein
(APPSwe/Ind) using a combination of histochemistry and stereologic techniques. Expression of
APPSwe/Ind in these mice is driven by a tetracycline-sensitive promoter. Tetracycline transcriptional
activator (tTA), the second transgene, is driven in turn by a CAM KIIa promoter that is only active in
neurons. Thus this double transgenic construct allows us to control expression of APPSwe/Ind with
doxycycline. Utilizing this characteristic, we created three distinct experimental groups: A, display abeta
plaque pathology and express APPSwe/Ind at time of sacrifice; B, display abeta plaque pathology but do
not express APPSwe/Ind at time of sacrifice; and C, do not display abeta plaque pathology but do
express APPSwe/Ind at time of sacrifice. Stereologic investigation revealed decreased hippocampal
volume in groups A(n=5) and B(n=5) when compared to group C(n=5) and age-matched wildtype (n=9)
