Lodato and Colleagues Investigate Neurodegeneration and DNA Mutations

Introduction to Neurodegeneration

Aging is commonly linked to a range of degenerative diseases in humans, prominently including neurodegeneration. This condition involves the deterioration of neuronal structure and function, potentially leading to neuron death. Notable neurodegenerative diseases include Alzheimer’s and Parkinson’s disease. For many years, scientists have proposed that mutations in neuronal DNA, which can occur throughout an individual’s life, may significantly contribute to the onset of neurodegeneration.

Research Overview

In a recent publication in *Science*, Lodato and his team from Harvard University examined this long-standing hypothesis. They sequenced the DNA of individual neurons from 15 healthy participants across different age groups, as well as from nine individuals diagnosed with Cockayne syndrome or xeroderma pigmentosa—two conditions known to induce neurodegeneration.

Findings on DNA Mutations

The researchers discovered that DNA mutations increased with age, with notable variation observed across different brain regions. Specifically, the hippocampal dentate gyrus, a region associated with Alzheimer’s disease, exhibited nearly double the number of mutations compared to the prefrontal cortex, which plays a crucial role in personality and decision-making. Moreover, individuals suffering from Cockayne syndrome or xeroderma pigmentosa presented with two to three times as many mutations as their healthy counterparts. Some mutations appeared to stem from fatty-acid oxidation, suggesting that the accumulation of mutations may occur exponentially rather than in a linear fashion.

Implications of the Research

The findings from Lodato and colleagues provide robust support for the theory that neurodegeneration is, at least in part, a consequence of DNA mutations within neurons. As these mutations are likely linked to oxidative processes, this insight may open new avenues for research and treatment strategies. Future investigations will be necessary to further elucidate the connection between these mutations and other neurodegenerative diseases, while also exploring potential treatment pathways.

Reference

Lodato et al. 2018. Aging and neurodegeneration are associated with increased mutations in single human neurons. *Science* 359(555-559).