Probability and Neurodegeneration: Alzheimer's Disease and Huntington's Disease.

BACKGROUND

The mechanisms by which sporadic young-onset neurodegenerative processes develop are uncertain.

METHODS

We have previously proposed that stochastic processes involving sequence changes at a DNA, RNA, or protein level in critical genes and proteins might be important to this process. Further investigation points to the contribution of probabilistic states in other factors involved in neurodegenerative conditions, such as-in the case of young onset Alzheimer's disease-head injury, apolipoprotein ε4 alleles and other elements that, by the interaction of conditional probabilities in these variables, influence the evolution of neurodegenerative conditions.

RESULTS

This proposal might help to explain why some autosomal dominant neurodegenerative conditions, such as trinucleotide repeat disorder (Huntington's disease), might have variable ages of onset given the same disease-causing CAG repeat mutation length.

CONCLUSIONS

The detection of somatic mutations in single brain cells provides some experimental support for these emerging concepts.