Title

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

Document Type

Article

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

Medical Subject Headings

Aging (metabolism, pathology); Alzheimer Disease (metabolism, pathology, prevention & control); Amyloid beta-Peptides (metabolism, toxicity); Animals; Brain (metabolism); Cells, Cultured; Disease Models, Animal; Disease Progression; Female; Hippocampus (cytology, drug effects); Humans; Male; Mice; Mice, Transgenic; Mole Rats; Neurons (drug effects)

Publication Date

10-1-2013

Publication Title

Neurobiology of aging

E-ISSN

1558-1497

Volume

34

Issue

10

First Page

2352

Last Page

60

PubMed ID

23618870

Digital Object Identifier (DOI)

10.1016/j.neurobiolaging.2013.03.032

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