Amylin challenge test and its correlation with brain imaging for Alzheimer’s disease

1813 Objectives Amylin, a pancreatic peptide, shares a β sheet structure with the amyloid-beta peptides (Aβ) present in the pathology of Alzheimer’s disease (AD). We tested whether amylin (or its analog pramlintide) may affect the homeostasis of Aβ in an animal model of AD, and in humans with cognitive defects. The human data was correlated with 18-FDG and AV-45 brain PET imaging because changes in plasma Aβ after amylin challenge may supplement imaging in the pre-mortem diagnosis of AD. Methods AD transgenic mice were injected intraperitoneally with amylin or pramlintide to study the effects on cognition, Aβ burden in the brain, and Aβ in the blood. A parallel experiment was conducted in human subjects who participated in the Alzheimer’s Disease Neuroimaging Initiative study. The human subjects were normal controls, suffered from amnestic mild cognitive impairment, or AD. They received a single subcutaneous injection of pramlintide and blood levels of Aβ were monitored, and correlated with 18-FDG and AV-45 brain PET scans. Results The amylin treatment significantly reduced the amyloid burden in the brain and improved learning and memory in the AD transgenic mouse model. A single injection of the drugs induced a surge of Aβ in serum with a magnitude proportional to the level of Aβ in brain tissue. In humans with cognitive defects the injection led to a drop in serum levels of Aβ, and this was weakly associated with imaging findings of the disease. Conclusions In a transgenic mouse model of AD amylin or pramlintide treatment results in changes in Aβ and cognition. In the few humans tested the blood levels of Aβ decreased, and these drops have a weak association with their abnormal cognition and PET imaging findings. Research Support NIA, AG-022476 and Ignition Award (W.Q.Q) and BU ADC pilot grant (H.Z). Support was also provided through P30 AG13864.