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 (APPswe/PS1dE9) 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-β (Aβ) plaque deposition, Aβ at blood vessel walls and biochemically measured levels of Aβ₁₋₄₀, Aβ₁₋₄₂ 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 Aβ deposition in parenchyma nor blood vessel walls.
Department of Anatomy, Donders Centre for Neuroscience, Radboud University Nijmegen Medical Centre, Geert Grooteplein Noord 21, 6525 EZ Nijmegen, The Netherlands.
Valerio
V
Zerbi
Diane
D
Jansen
Pieter J
PJ
Dederen
Andor
A
Veltien
Bob
B
Hamans
Yang
Y
Liu
Arend
A
Heerschap
Amanda J
AJ
Kiliaan
D000375:Aging / Q000502:physiology*; D000544:Alzheimer Disease / Q000150:complications*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D001811:Blood Volume Determination; D054022:Cerebrum / Q000098:blood supply*; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging / Q000379:methods; D051379:Mice; D008822:Mice, Transgenic; D055806:Microvessels / Q000503:physiopathology*; D023421:Models, Animal; D053764:Presenilin-1 / Q000235:genetics; D014652:Vascular Diseases / Q000150:complications*
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D051272:Glucose Transporter Type 1; C508853:PSEN1 protein, human; D053764:Presenilin-1; C495678:Slc2a1 protein, mouse