Neuroprotective effects of the amylin analogue pramlintide on Alzheimer's disease pathogenesis and cognition

Brittany L. Adler, Mark Yarchoan, Hae Min Hwang, Natalia Louneva, Jeffrey A. Blair, Russell Palm, Mark A. Smith, Hyoung gon Lee, Steven E. Arnold, Gemma Casadesus

Research output: Contribution to journalArticle

Abstract

Amylin is a metabolic peptide hormone that is co-secreted with insulin from beta cells in the pancreas and activates many of the downstream targets of insulin. To investigate the relationship between this hormone and Alzheimer's disease (AD), we measured plasma human amylin levels in 206 subjects with AD, 64 subjects with mild cognitive impairment, and 111 subjects with no cognitive impairment and found significantly lower amylin levels among subjects with AD and mild cognitive impairment compared with the cognitively intact subjects. To investigate mechanisms underlying amylin's effects in the brain, we administered chronic infusions of the amylin analog pramlintide in the senescence-accelerated prone mouse, a mouse model of sporadic AD. Pramlintide administration improved performance in the novel object recognition task, a validated test of memory and cognition. The pramlintide-treated mice had increased expression of the synaptic marker synapsin I and the kinase cyclin-dependent kinase-5 in the hippocampus, as well as decreased oxidative stress and inflammatory markers in the hippocampus. A dose-dependent increase in cyclin-dependent kinase-5 and activation of extracellular-signal-regulated-kinases 1/2 by pramlintide treatment invitro was also present indicating functionality of the amylin receptor in neurons. Together these results suggest that amylin analogs have neuroprotective properties and might be of therapeutic benefit in AD.

Original languageEnglish (US)
Pages (from-to)793-801
Number of pages9
JournalNeurobiology of Aging
Volume35
Issue number4
DOIs
StatePublished - Apr 1 2014
Externally publishedYes

Keywords

  • Alzheimer's disease
  • Amylin
  • CDK5
  • Diabetes
  • IAPP
  • Incretin
  • Insulin
  • Pramlintide
  • SAMP8
  • Synaptic plasticity

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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  • Cite this

    Adler, B. L., Yarchoan, M., Hwang, H. M., Louneva, N., Blair, J. A., Palm, R., Smith, M. A., Lee, H. G., Arnold, S. E., & Casadesus, G. (2014). Neuroprotective effects of the amylin analogue pramlintide on Alzheimer's disease pathogenesis and cognition. Neurobiology of Aging, 35(4), 793-801. https://doi.org/10.1016/j.neurobiolaging.2013.10.076