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CEREBRAL PERFUSION IN THE 5XFAD MOUSE MODEL OF ALZHEIMER’S DISEASE

      Background

      The need for early, definitive diagnosis of Alzheimer’s disease (AD) is imperative for disease management, and will increasingly rely on improved neuroimaging techniques. Functional neuroimaging with 99mTc-hexamethylpropylamino-oxime (99mTc-HMPAO) SPECT has been used as an ancillary test in AD to evaluate cerebral blood flow. Specific patterns of hypoperfusion and hypometabolism have been established in human AD using 99mTc-HMPAO-SPECT and 18FDG-PET, respectively. Hypometabolism has been observed in the 5XFAD mouse; however, it is unknown whether hypoperfusion signatures of AD are also present in 5XFAD, often used for diagnostic/therapeutic drug development. We seek to assess baseline perfusion in the 5XFAD mouse using 99mTc-HMPAO SPECT and determine whether perfusion signatures of human AD are recapitulated in this model.

      Methods

      Male 5XFAD (n=3) and age-matched wild-type (WT) (n=2) mice at 12 months underwent SPECT scanning 20min after 99mTc-HMPAO administration and subsequently imaged using CT/MRI. Whole brain standardized uptake values (SUVs) were compared.

      Results

      Preliminary results indicate that, in the 5XFAD brain, patterns of hyperperfusion, rather than hypoperfusion are seen with significantly greater (60%) whole brain SUVs observed in 5XFAD compared to WT (p=0.009).

      Conclusions

      Early evidence suggests an apparent disconnect between cerebral blood flow and glucose metabolism (neurovascular decoupling) in the 5XFAD brain. A full study to establish regional patterns of perfusion in 5XFAD mice is warranted to further evaluate disease progression in this model. Establishing these baseline perfusion patterns is extremely valuable and identifying discrepancies from human AD should be taken under advisement in pre-clinical diagnostic and therapeutic drug discovery programs.