Pramlintide: The Effects of a Single Drug Injection on Blood Phosphatidylcholine Profile for Alzheimer’s Disease

Article type: Research Article

Authors: Tao, Qiushan^a | Zhu, Haihao^a | Chen, Xi^a | Stern, Robert A.^{b; c; d} | Kowall, Neil^{b; d} | Au, Rhoda^{b; f} | Blusztajn, Jan Krzysztof^e | Qiu, Wei Qiao^{a; d; g; *} | for the Alzheimer’s Disease Metabolomics Consortium¹

Affiliations: [a] Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, USA | [b] Neurology, Boston University School of Medicine, Boston, MA, USA | [c] Neurosurgery, Boston University School of Medicine, Boston, MA, USA | [d] Alzheimer’s Disease Center, Boston University School of Medicine, Boston, MA, USA | [e] Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA, USA | [f] Departments of Anatomy and Neurobiology, Boston University School of Medicine, Boston, MA, USA | [g] Departments of Psychiatry, Boston University School of Medicine, Boston, MA, USA

Correspondence: [*] Correspondence to: Wendy Wei Qiao Qiu, MD, PhD, Boston University School of Medicine, 72 East Concord Street, R-623D, Boston, MA 02118, USA. Tel.: +1 617 638 4336; Fax: +1 617 638 5254; E-mail: [email protected].

Note: [1] Data used in preparation of this article were generated by the Alzheimer’s Disease Metabolomics Consortium (ADMC). As such, the investigators within the ADMC provided data but did not participate in analysis or writing of this report. A complete listing of ADMC investigators can be found at: https://sites.duke.edu/adnimetab/about-us/the-team/

Abstract: Studies suggest that a single injection of pramlintide, an amylin analog, induces changes in Alzheimer’s disease (AD) biomarkers in the blood of AD mouse models and AD patients. The aim of this study was to examine whether a pramlintide challenge combined with a phosphatidylcholine (PC) profile diagnoses of AD and mild cognitive impairment (MCI) better than PC alone. Non-diabetic subjects with cognitive status were administered a single subcutaneous injection of 60 mcg of pramlintide under fasting condition. A total of 71 PCs, amyloid-β peptide (Aβ), and total tau (t-tau) in plasma at different time points were measured and treated as individual variables. A single injection of pramlintide altered the levels of 7 PCs in the blood, while a pramlintide injection plus food modulated the levels of 10 PCs in the blood (p < 0.05). The levels of 2 PCs in MCI and 12 PCs in AD in the pramlintide challenge were significantly lower than the ones in controls. We found that while some PCs were associated with only Aβ levels, other PCs were associated with both Aβ and t-tau levels. A receiver operating characteristic analysis of the PCs was combined with the Aβ and t-tau data to produce an area under the curve predictive value of 0.9799 between MCI subjects and controls, 0.9794 between AD subjects and controls, and 0.9490 between AD and MCI subjects. A combination of AD biomarkers and a group of PCs post a pramlintide challenge may provide a valuable diagnostic and prognostic test for AD and MCI.

Keywords: Alzheimer’s disease, amylin, mild cognitive impairment, phosphatidylcholine, pramlintide

DOI: 10.3233/JAD-170948

Journal: Journal of Alzheimer's Disease, vol. 62, no. 2, pp. 597-609, 2018