Microvascular cerebral blood volume changes in aging APP(swe)/PS1 (dE9) AD mouse model: a voxel-wise approach

Vascular disorders can either be cause or consequence in the pathophysiology of Alzheimer's disease (AD). To comprehensively characterize the occurrence of vascular impairment in a double transgenic mouse model for AD (APP(swe)/PS1(dE9)) during aging, we developed a new method to obtain microvascular relative cerebral blood volume (rCBV(micro)) maps from gradient echo MR imaging by histogram evaluation and we applied a voxel-wise approach to detect rCBV(micro) changes. With this methodology the development of cerebral microvascular impairments can be described in vivo with 0.16�mm isotropic resolution for the whole mouse brain. At 8�months, impaired rCBV(micro) appeared in some cortical regions and in the thalamus, which spreads over several sub-cortical areas and the hippocampus at 13�months. With a ROI-based approach, we further showed that hippocampal rCBV(micro) in 13-month-old wild-type and APP(swe)/PS1(dE9) mice correlates well with capillary density measured with immunohistochemical staining. However, no differences in capillary density were detected between genotypes. The rCBV(micro) values showed no significant correlation with amyloid-� (A�) plaque deposition, A� at blood vessel walls and biochemically measured levels of A�(1-40), A�(1-42) oligomers and fibrillar forms. These results suggest that rCBV(micro) reduction is caused by an impaired vasoactivity of capillaries and arterioles, which is not directly correlated with the amount of A� deposition in parenchyma nor blood vessel walls