Amyloid beta and the longest-lived rodent: the naked mole-rat as a model for natural protection from Alzheimer%26apos;s disease

作者：Edrey Yael H; Medina David X; Gaczynska Maria; Osmulski Pawel A; Oddo Salvatore; Caccamo Antonella; Buffenstein Rochelle^*

来源：Neurobiology of Aging, 2013, 34(10): 2352-2360.

DOI：10.1016/j.neurobiolaging.2013.03.032

• Alzheimer%26apos
• s disease
• Amyloid beta
• Naked mole-rat
• Aggregation
• Neuronal toxicity
• 3xTg-AD mice
• Heterocephalus glaber

Amyloid beta (A beta) is implicated in Alzheimer%26apos;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 A beta 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 A beta levels in the individuals examined (2-20+ years). The NMR A beta 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 A beta was less prone to aggregation than human A beta. Nevertheless, both NMR and human A beta were equally toxic to mouse hippocampal neurons, suggesting that A beta neurotoxicity and aggregation properties were not coupled. Understanding how NMRs acquire and tolerate high levels of A beta with no plaque formation could provide useful insights into AD, and may elucidate protective mechanisms that delay AD progression.

• 出版日期2013-10