Author:
DeBay Drew R.,Phi Tân-Trào,Bowen Chris V.,Burrell Steven C.,Darvesh Sultan
Abstract
AbstractNeuroimaging with [2,2-dimethyl-3-[(2R,3E)-3-oxidoiminobutan-2-yl]azanidylpropyl]-[(2R,3E)-3-hydroxyiminobutan-2-yl]azanide;oxo(99Tc)technetium-99(3+) ([99mTc]HMPAO) single photon emission computed tomography (SPECT) is used in Alzheimer’s disease (AD) to evaluate regional cerebral blood flow (rCBF). Hypoperfusion in select temporoparietal regions has been observed in human AD. However, it is unknown whether AD hypoperfusion signatures are also present in the 5XFAD mouse model. The current study was undertaken to compare baseline brain perfusion between 5XFAD and wild-type (WT) mice using [99mTc]HMPAO SPECT and determine whether hypoperfusion is recapitulated in 5XFAD mice. 5XFAD and WT mice underwent a 45 min SPECT scan, 20 min after [99mTc]HMPAO administration. Whole brain and regional standardized uptake values (SUV) and regional relative standardized uptake values (SUVR) with whole brain reference were compared between groups. Brain perfusion was similar between WT and 5XFAD brains. Whole brain [99mTc]HMPAO retention revealed no significant difference in SUV (5XFAD, 0.372 ± 0.762; WT, 0.640 ± 0.955; p = 0.536). Similarly, regional analysis revealed no significant differences in [99mTc]HMPAO metrics between groups (SUV: 0.357 ≤ p ≤ 0.640; SUVR: 0.595 ≤ p ≤ 0.936). These results suggest apparent discrepancies in rCBF between human AD and the 5XFAD model. Establishing baseline perfusion patterns in 5XFAD mice is essential to inform pre-clinical diagnostic and therapeutic drug discovery programs.
Funder
Faculty of Medicine, Dalhousie University
Mitacs
Research Nova Scotia
Natural Sciences and Engineering Research Council of Canada
Killam Trusts
Dalhousie Medical Research Foundation
Canadian Institutes of Health Research
Publisher
Springer Science and Business Media LLC
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