Vascular endothelial growth factor associated dissimilar cerebrovascular phenotypes in two different mouse models of Alzheimer's Disease.

Publication Type	Academic Article
Authors	Tataryn N, Singh V, Dyke J, Berk-Rauch H, Clausen D, Aronowitz E, Norris E, Strickland S, Ahn H
Journal	Neurobiol Aging
Volume	107
Pagination	96-108
Date Published	07/28/2021
ISSN	1558-1497
Keywords	Alzheimer Disease, Vascular Endothelial Growth Factor A
Abstract	Vascular perturbations and cerebral hypometabolism are emerging as important components of Alzheimer's disease (AD). While various in vivo imaging modalities have been designed to detect changes of cerebral perfusion and metabolism in AD patients and animal models, study results were often heterogenous with respect to imaging techniques and animal models. We therefore evaluated cerebral perfusion and glucose metabolism of two popular transgenic AD mouse strains, TgCRND8 and 5xFAD, at 7 and 12 months-of-age under identical conditions and analyzed possible molecular mechanisms underlying heterogeneous cerebrovascular phenotypes. Results revealed disparate findings in these two strains, displaying important aspects of AD progression. TgCRND8 mice showed significantly decreased cerebral blood flow and glucose metabolism with unchanged cerebral blood volume (CBV) at 12 months-of-age whereas 5xFAD mice showed unaltered glucose metabolism with significant increase in CBV at 12 months-of-age and a biphasic pattern of early hypoperfusion followed by a rebound to normal cerebral blood flow in late disease. Finally, immunoblotting assays suggested that VEGF dependent vascular tone change may restore normoperfusion and increase CBV in 5xFAD.
DOI	10.1016/j.neurobiolaging.2021.07.015
PubMed ID	34416494
PubMed Central ID	PMC8595520