Amyloid beta and the longest-lived rodent: The naked mole-rat as a model for natural protection from alzheimer's disease

Yael H. Edrey, David X. Medina, Maria Gaczynska, Pawel A. Osmulski, Salvatore Oddo, Antonella Caccamo, Rochelle Buffenstein

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Amyloid beta (Aβ) is implicated in Alzheimer's disease (AD) as an integral component of both neural toxicity and plaque formation. Brains of the longest-lived rodents, naked mole-rats (NMRs) approximately 32 years of age, had levels of Aβ similar to those of the 3xTg-AD mouse model of AD. Interestingly, there was no evidence of extracellular plaques, nor was there an age-related increase in Aβ levels in the individuals examined (2-20+ years). The NMR Aβ peptide showed greater homology to the human sequence than to the mouse sequence, differing by only 1 amino acid from the former. This subtle difference led to interspecies differences in aggregation propensity but not neurotoxicity; NMR Aβ was less prone to aggregation than human Aβ. Nevertheless, both NMR and human Aβ were equally toxic to mouse hippocampal neurons, suggesting that Aβ neurotoxicity and aggregation properties were not coupled. Understanding how NMRs acquire and tolerate high levels of Aβ with no plaque formation could provide useful insights into AD, and may elucidate protective mechanisms that delay AD progression.

Original languageEnglish (US)
Pages (from-to)2352-2360
Number of pages9
JournalNeurobiology of Aging
Volume34
Issue number10
DOIs
StatePublished - Oct 2013

Keywords

  • 3xTg-AD mice
  • Aggregation
  • Alzheimer's disease
  • Amyloid beta
  • Heterocephalus glaber
  • Naked mole-rat
  • Neuronal toxicity

ASJC Scopus subject areas

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

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