An amylin analog used as a challenge test for Alzheimer's disease

Haihao Zhu; Robert A. Stern; Qiushan Tao; Alexandra Bourlas; Maritza D. Essis; Meenakshi Chivukula; James Rosenzweig; Devin Steenkamp; Weiming Xia; Gustavo A. Mercier; Yorghos Tripodis; Martin Farlow; Neil Kowall; Wei Qiao Qiu

doi:10.1016/j.trci.2016.12.002

An amylin analog used as a challenge test for Alzheimer's disease

Haihao Zhu, Robert A. Stern, Qiushan Tao, Alexandra Bourlas, Maritza D. Essis, Meenakshi Chivukula, James Rosenzweig, Devin Steenkamp, Weiming Xia, Gustavo A. Mercier, Yorghos Tripodis, Martin Farlow, Neil Kowall, Wei Qiao Qiu

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Abstract

Introduction Preclinical studies demonstrate the potential of amylin in the diagnosis of Alzheimer's disease (AD). We aimed to lay the foundation for repurposing the amylin analog and a diabetes drug, pramlintide, for AD in humans. Methods We administered a single subcutaneous injection of 60 μg of pramlintide to nondiabetic subjects under fasting conditions. Results None of the participants developed hypoglycemia after the injection of pramlintide. The pramlintide challenge induced a significant surge of amyloid-β peptide and a decrease in total tau in the plasma of AD subjects but not in control participants. The pramlintide injection provoked an increase in interleukin 1 receptor antagonist and a decrease in retinol-binding protein 4, which separates AD subjects from control subjects. Discussion Pramlintide use appeared to be safe in the absence of diabetes. The biomarker changes as a result of the pramlintide challenge, which distinguished AD from control subjects and mild cognitive impairment.

Original language	English (US)
Pages (from-to)	33-43
Number of pages	11
Journal	Alzheimer's and Dementia: Translational Research and Clinical Interventions
Volume	3
Issue number	1
DOIs	https://doi.org/10.1016/j.trci.2016.12.002
State	Published - Jan 1 2017

Keywords

Alzheimer's disease (AD)
Amylin challenge
Biomarkers
Diagnosis
Pramlintide
Safety

ASJC Scopus subject areas

Clinical Neurology
Psychiatry and Mental health

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10.1016/j.trci.2016.12.002

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Zhu, H., Stern, R. A., Tao, Q., Bourlas, A., Essis, M. D., Chivukula, M., Rosenzweig, J., Steenkamp, D., Xia, W., Mercier, G. A., Tripodis, Y., Farlow, M., Kowall, N., & Qiu, W. Q. (2017). An amylin analog used as a challenge test for Alzheimer's disease. Alzheimer's and Dementia: Translational Research and Clinical Interventions, 3(1), 33-43. https://doi.org/10.1016/j.trci.2016.12.002

Zhu, H, Stern, RA, Tao, Q, Bourlas, A, Essis, MD, Chivukula, M, Rosenzweig, J, Steenkamp, D, Xia, W, Mercier, GA, Tripodis, Y, Farlow, M, Kowall, N & Qiu, WQ 2017, 'An amylin analog used as a challenge test for Alzheimer's disease', Alzheimer's and Dementia: Translational Research and Clinical Interventions, vol. 3, no. 1, pp. 33-43. https://doi.org/10.1016/j.trci.2016.12.002

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abstract = "Introduction Preclinical studies demonstrate the potential of amylin in the diagnosis of Alzheimer's disease (AD). We aimed to lay the foundation for repurposing the amylin analog and a diabetes drug, pramlintide, for AD in humans. Methods We administered a single subcutaneous injection of 60 μg of pramlintide to nondiabetic subjects under fasting conditions. Results None of the participants developed hypoglycemia after the injection of pramlintide. The pramlintide challenge induced a significant surge of amyloid-β peptide and a decrease in total tau in the plasma of AD subjects but not in control participants. The pramlintide injection provoked an increase in interleukin 1 receptor antagonist and a decrease in retinol-binding protein 4, which separates AD subjects from control subjects. Discussion Pramlintide use appeared to be safe in the absence of diabetes. The biomarker changes as a result of the pramlintide challenge, which distinguished AD from control subjects and mild cognitive impairment.",

keywords = "Alzheimer's disease (AD), Amylin challenge, Biomarkers, Diagnosis, Pramlintide, Safety",

author = "Haihao Zhu and Stern, {Robert A.} and Qiushan Tao and Alexandra Bourlas and Essis, {Maritza D.} and Meenakshi Chivukula and James Rosenzweig and Devin Steenkamp and Weiming Xia and Mercier, {Gustavo A.} and Yorghos Tripodis and Martin Farlow and Neil Kowall and Qiu, {Wei Qiao}",

note = "Funding Information: This work was supported by grants from the Alzheimer's Disease Association (IIRG-13-284238), NIA (R21 AG045757A1), and Ignition Award (to W.Q.Q), and from Boston University Alzheimer's Disease Center pilot grant (to H.Z.). Publisher Copyright: {\textcopyright} 2017 The Authors",

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doi = "10.1016/j.trci.2016.12.002",

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T1 - An amylin analog used as a challenge test for Alzheimer's disease

AU - Zhu, Haihao

AU - Stern, Robert A.

AU - Tao, Qiushan

AU - Bourlas, Alexandra

AU - Essis, Maritza D.

AU - Chivukula, Meenakshi

AU - Rosenzweig, James

AU - Steenkamp, Devin

AU - Xia, Weiming

AU - Mercier, Gustavo A.

AU - Tripodis, Yorghos

AU - Farlow, Martin

AU - Kowall, Neil

AU - Qiu, Wei Qiao

N1 - Funding Information: This work was supported by grants from the Alzheimer's Disease Association (IIRG-13-284238), NIA (R21 AG045757A1), and Ignition Award (to W.Q.Q), and from Boston University Alzheimer's Disease Center pilot grant (to H.Z.). Publisher Copyright: © 2017 The Authors

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Introduction Preclinical studies demonstrate the potential of amylin in the diagnosis of Alzheimer's disease (AD). We aimed to lay the foundation for repurposing the amylin analog and a diabetes drug, pramlintide, for AD in humans. Methods We administered a single subcutaneous injection of 60 μg of pramlintide to nondiabetic subjects under fasting conditions. Results None of the participants developed hypoglycemia after the injection of pramlintide. The pramlintide challenge induced a significant surge of amyloid-β peptide and a decrease in total tau in the plasma of AD subjects but not in control participants. The pramlintide injection provoked an increase in interleukin 1 receptor antagonist and a decrease in retinol-binding protein 4, which separates AD subjects from control subjects. Discussion Pramlintide use appeared to be safe in the absence of diabetes. The biomarker changes as a result of the pramlintide challenge, which distinguished AD from control subjects and mild cognitive impairment.

AB - Introduction Preclinical studies demonstrate the potential of amylin in the diagnosis of Alzheimer's disease (AD). We aimed to lay the foundation for repurposing the amylin analog and a diabetes drug, pramlintide, for AD in humans. Methods We administered a single subcutaneous injection of 60 μg of pramlintide to nondiabetic subjects under fasting conditions. Results None of the participants developed hypoglycemia after the injection of pramlintide. The pramlintide challenge induced a significant surge of amyloid-β peptide and a decrease in total tau in the plasma of AD subjects but not in control participants. The pramlintide injection provoked an increase in interleukin 1 receptor antagonist and a decrease in retinol-binding protein 4, which separates AD subjects from control subjects. Discussion Pramlintide use appeared to be safe in the absence of diabetes. The biomarker changes as a result of the pramlintide challenge, which distinguished AD from control subjects and mild cognitive impairment.

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An amylin analog used as a challenge test for Alzheimer's disease

Abstract

Keywords

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