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

31 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Mole Rats
Amyloid
Rodentia
Alzheimer Disease
Poisons
Disease Progression
Neurons
Amino Acids
Peptides
Brain

Keywords

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

ASJC Scopus subject areas

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

Cite this

Amyloid beta and the longest-lived rodent : The naked mole-rat as a model for natural protection from alzheimer's disease. / Edrey, Yael H.; Medina, David X.; Gaczynska, Maria; Osmulski, Pawel A.; Oddo, Salvatore; Caccamo, Antonella; Buffenstein, Rochelle.

In: Neurobiology of Aging, Vol. 34, No. 10, 10.2013, p. 2352-2360.

Research output: Contribution to journalArticle

Edrey, Yael H. ; Medina, David X. ; Gaczynska, Maria ; Osmulski, Pawel A. ; Oddo, Salvatore ; Caccamo, Antonella ; Buffenstein, Rochelle. / Amyloid beta and the longest-lived rodent : The naked mole-rat as a model for natural protection from alzheimer's disease. In: Neurobiology of Aging. 2013 ; Vol. 34, No. 10. pp. 2352-2360.
@article{abddb5de7e584773a87e0e3fab94b840,
title = "Amyloid beta and the longest-lived rodent: The naked mole-rat as a model for natural protection from alzheimer's disease",
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.",
keywords = "3xTg-AD mice, Aggregation, Alzheimer's disease, Amyloid beta, Heterocephalus glaber, Naked mole-rat, Neuronal toxicity",
author = "Edrey, {Yael H.} and Medina, {David X.} and Maria Gaczynska and Osmulski, {Pawel A.} and Salvatore Oddo and Antonella Caccamo and Rochelle Buffenstein",
year = "2013",
month = "10",
doi = "10.1016/j.neurobiolaging.2013.03.032",
language = "English (US)",
volume = "34",
pages = "2352--2360",
journal = "Neurobiology of Aging",
issn = "0197-4580",
publisher = "Elsevier Inc.",
number = "10",

}

TY - JOUR

T1 - Amyloid beta and the longest-lived rodent

T2 - The naked mole-rat as a model for natural protection from alzheimer's disease

AU - Edrey, Yael H.

AU - Medina, David X.

AU - Gaczynska, Maria

AU - Osmulski, Pawel A.

AU - Oddo, Salvatore

AU - Caccamo, Antonella

AU - Buffenstein, Rochelle

PY - 2013/10

Y1 - 2013/10

N2 - 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.

AB - 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.

KW - 3xTg-AD mice

KW - Aggregation

KW - Alzheimer's disease

KW - Amyloid beta

KW - Heterocephalus glaber

KW - Naked mole-rat

KW - Neuronal toxicity

UR - http://www.scopus.com/inward/record.url?scp=84879879778&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84879879778&partnerID=8YFLogxK

U2 - 10.1016/j.neurobiolaging.2013.03.032

DO - 10.1016/j.neurobiolaging.2013.03.032

M3 - Article

VL - 34

SP - 2352

EP - 2360

JO - Neurobiology of Aging

JF - Neurobiology of Aging

SN - 0197-4580

IS - 10

ER -