Alterations in cerebral blood flow and glucose utilization in mice overexpressing the amyloid precursor protein

We have used quantitative autoradiographic techniques to study the relationship between cerebral blood flow (CBF) and glucose utilization (CGU) in two lines of transgenic mice overexpressing Swedish mutant amyloid precursor protein (APP) and APP-derived Abeta peptides. Mice were studied at an age when there are no amyloid plaques. In the 2123 line, CBF was reduced only in telencephalic regions with no corresponding decrease in CGU. In 2576 transgenics, a line with higher levels of Abeta peptide, both CBF and CGU were reduced throughout the brain. The data indicate that Abeta induces alterations in resting CBF that are either associated with or independent of alterations in CGU and that occur in the absence of amyloid deposition in neuropil of blood vessels. These observations support the hypothesis that cerebrovascular and metabolic abnormalities are early events in the pathogenesis of Alzheimer's disease. (C) 2002 Elsevier Science (USA).