Islet amyloid polypeptide (iapp): A second amyloid in alzheimer’s disease

Janelle N. Fawver, Yonatan Ghiwot, Catherine Koola, Wesley Carrera, Jennifer Rodriguez-Rivera, Caterina M. Hernandez, Kelly T. Dineley, Yu Kong, Jianrong Li, Jack Jhamandas, George Perry, Ian V.J. Murray

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Amyloid formation is the pathological hallmark of type 2 diabetes (T2D) and Alzheimer’s disease (AD). These diseases are marked by extracellular amyloid deposits of islet amyloid polypeptide (IAPP) in the pancreas and amyloid _ (A_) in the brain. Since IAPP may enter the brain and disparate amyloids can cross-seed each other to augment amyloid formation, we hypothesized that pancreatic derived IAPP may enter the brain to augment misfolding of A_ in AD. The corollaries for validity of this hypothesis are that IAPP [1] enters the brain, [2] augments A_ misfolding, [3] associates with A_ plaques, and most importantly [4] plasma levels correlate with AD diagnosis. We demonstrate the first 3 corollaries that: (1) IAPP is present in the brain in human cerebrospinal fluid (CSF), (2) synthetic IAPP promoted oligomerization of A_ in vitro, and (3) endogenous IAPP localized to A_ oligomers and plaques. For the 4th corollary, we did not observe correlation of peripheral IAPP levels with AD pathology in either an African American cohort or AD transgenic mice. In the African American cohort, with increased risk for both T2D and AD, peripheral IAPP levels were not significantly different in samples with no disease, T2D, AD, or both T2D and AD. In the Tg2576 AD mouse model, IAPP plasma levels were not significantly elevated at an age where the mice exhibit the glucose intolerance of pre-diabetes. Based on this negative data, it appears unlikely that peripheral IAPP cross-seeds or “infects” A_ pathology in AD brain. However, we provide novel and additional data which demonstrate that IAPP protein is present in astrocytes in murine brain and secreted from primary cultured astrocytes. This preliminary report suggests a potential and novel association between brain derived IAPP and AD, however whether astrocytic derived IAPP cross-seeds A_ in the brain requires further research.

Original languageEnglish (US)
Pages (from-to)928-940
Number of pages13
JournalCurrent Alzheimer Research
Volume11
Issue number10
DOIs
StatePublished - Dec 1 2014

Fingerprint

Islet Amyloid Polypeptide
Amyloid
Alzheimer Disease
Brain
Type 2 Diabetes Mellitus
Seeds
Astrocytes
African Americans
Pathology
Amyloidogenic Proteins
Glucose Intolerance
Amyloid Plaques
Islets of Langerhans

Keywords

  • Alzheimer's disease
  • Amylin
  • Amyloid beta
  • Blood
  • Brain
  • Immunohistochemistry
  • Metabolic dysfunction
  • Oligomers
  • Plaques
  • Type 2 diabetes

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Fawver, J. N., Ghiwot, Y., Koola, C., Carrera, W., Rodriguez-Rivera, J., Hernandez, C. M., ... Murray, I. V. J. (2014). Islet amyloid polypeptide (iapp): A second amyloid in alzheimer’s disease. Current Alzheimer Research, 11(10), 928-940. https://doi.org/10.2174/1567205011666141107124538

Islet amyloid polypeptide (iapp) : A second amyloid in alzheimer’s disease. / Fawver, Janelle N.; Ghiwot, Yonatan; Koola, Catherine; Carrera, Wesley; Rodriguez-Rivera, Jennifer; Hernandez, Caterina M.; Dineley, Kelly T.; Kong, Yu; Li, Jianrong; Jhamandas, Jack; Perry, George; Murray, Ian V.J.

In: Current Alzheimer Research, Vol. 11, No. 10, 01.12.2014, p. 928-940.

Research output: Contribution to journalArticle

Fawver, JN, Ghiwot, Y, Koola, C, Carrera, W, Rodriguez-Rivera, J, Hernandez, CM, Dineley, KT, Kong, Y, Li, J, Jhamandas, J, Perry, G & Murray, IVJ 2014, 'Islet amyloid polypeptide (iapp): A second amyloid in alzheimer’s disease', Current Alzheimer Research, vol. 11, no. 10, pp. 928-940. https://doi.org/10.2174/1567205011666141107124538
Fawver JN, Ghiwot Y, Koola C, Carrera W, Rodriguez-Rivera J, Hernandez CM et al. Islet amyloid polypeptide (iapp): A second amyloid in alzheimer’s disease. Current Alzheimer Research. 2014 Dec 1;11(10):928-940. https://doi.org/10.2174/1567205011666141107124538
Fawver, Janelle N. ; Ghiwot, Yonatan ; Koola, Catherine ; Carrera, Wesley ; Rodriguez-Rivera, Jennifer ; Hernandez, Caterina M. ; Dineley, Kelly T. ; Kong, Yu ; Li, Jianrong ; Jhamandas, Jack ; Perry, George ; Murray, Ian V.J. / Islet amyloid polypeptide (iapp) : A second amyloid in alzheimer’s disease. In: Current Alzheimer Research. 2014 ; Vol. 11, No. 10. pp. 928-940.
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