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Cited by 108Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Intraperitoneal injection of the pancreatic peptide amylin potently reduces behavioral impairment and brain amyloid pathology in murine models of Alzheimer’s disease

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Zhu, H, Wang, X, Wallack, M, Li, H, Carreras, I, Dedeoglu, A, Hur, J-Y, Zheng, H +7 more·2015·Molecular Psychiatry
DOI 10.1038/mp.2014.17PMC PMC4161670
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Abstract

Amylin, a pancreatic peptide, and amyloid-beta peptides (Aβ), a major component of Alzheimer's disease (AD) brain, share similar β-sheet secondary structures, but it is not known whether pancreatic amylin affects amyloid pathogenesis in the AD brain. Using AD mouse models, we investigated the effects of amylin and its clinical analog, pramlintide, on AD pathogenesis. Surprisingly, chronic intraperitoneal (i.p.) injection of AD animals with either amylin or pramlintide reduces the amyloid burden as well as lowers the concentrations of Aβ in the brain. These treatments significantly improve their learning and memory assessed by two behavioral tests, Y maze and Morris water maze. Both amylin and pramlintide treatments increase the concentrations of Aβ1-42 in cerebral spinal fluid (CSF). A single i.p. injection of either peptide also induces a surge of Aβ in the serum, the magnitude of which is proportionate to the amount of Aβ in brain tissue. One intracerebroventricular injection of amylin induces a more significant surge in serum Aβ than one i.p. injection of the peptide. In 330 human plasma samples, a positive association between amylin and Aβ1-42 as well as Aβ1-40 is found only in patients with AD or amnestic mild cognitive impairment. As amylin readily crosses the blood-brain barrier, our study demonstrates that peripheral amylin's action on the central nervous system results in translocation of Aβ from the brain into the CSF and blood that could be an explanation for a positive relationship between amylin and Aβ in blood. As naturally occurring amylin may play a role in regulating Aβ in brain, amylin class peptides may provide a new avenue for both treatment and diagnosis of AD.

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  • Loss of spines from newly evolved cognitive circuits in schizophrenia likely contributes to their profound hypoactivity.

    “The loss of spines from newly evolved cognitive circuits in schizophrenia likely contributes to their profound hypoactivity119.”

    From Stress weakens prefrontal networks: molecular insults to higher cognition (2015) · cites this paper as [119]

    The Discussion describes amylin treatment and amyloid pathology in Alzheimer’s disease mice, not spine loss or circuit hypoactivity in schizophrenia. Searches for schizophrenia, dendritic spines, and hypoactivity found no passage in our copy addressing the claim. (LLM, conf=0.75)

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Authors
Zhu, H., Wang, X., Wallack, M., Li, H., Carreras, I., Dedeoglu, A., Hur, J.-Y., Zheng, H., Li, H., Fine, R., Mwamburi, M., Sun, X., Kowall, N., Stern, R. A., & Qiu, W. Q.
Affiliations
  • Boston University (US)
  • Memorial Sloan Kettering Cancer Center (US)
  • Baylor College of Medicine (US)
  • Tufts University (US)
Corresponding author
Qiu, W Q
ORCID
Venue
Molecular Psychiatry
Publisher
Springer Science and Business Media LLC
Published
2014-03-11
Volume
20
Issue
2
Pages
252-262
ISSN
  • 1359-4184 (ISSN-L)
  • 1476-5578
DOI
10.1038/mp.2014.17
PMC
PMC4161670
OpenAlex
W2065714314
Cited by
108
References
4
Citations by year
2026: 4 · 2025: 9 · 2024: 7 · 2023: 7 · 2022: 3 · 2021: 10 · 2020: 12 · 2019: 13 · 2018: 10 · 2017: 13 · 2016: 6 · 2015: 9 · 2014: 5
FWCI
7.33
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Psychiatry (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
National Institute on Aging (P30 AG13864, AG‐022476, K24AG050842, K23AG022476, R01AG031171, R21AG045757, P30AG013846)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
amylin, pramlintide, Alzheimer's disease, amyloid-beta, amyloid-beta 42, amyloid-β1-40, blood-brain barrier, cerebrospinal fluid, learning and memory impairment, intraperitoneal injection, intracerebroventricular administration, amnestic mild cognitive impairment
MeSH terms
Alzheimer Disease, Animals, Mental Disorders, Disease Models, Animal, Female, Gene Expression Regulation, Humans, Male, Mice, Inbred C57BL, Mice, Transgenic, Mutation, Peptide Fragments, Psychiatric Status Rating Scales, Amyloid beta-Peptides, Aspartic Acid Endopeptidases, Amyloid beta-Protein Precursor, Maze Learning, Mice, Presenilin-1, Amyloid Precursor Protein Secretases, Islet Amyloid Polypeptide, Amylin Receptor Agonists

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