This important study establishes for the first time a genetic risk factor for sporadic ALS, thus providing a long-sought entry point into mechanisms and genetics of ALS. Genetic risk factors for neurodegenerative diseases will likely lead to novel insights into mechanisms of disease.
The impact of the chromogranin B mutations is slightly lower than that of the ApoE4 allele in Alzheimer disease. Because the chromogranin B mutations had an impact on onset time in familial ALS, and on risk of disease in sporadic ALS, the findings provide important support for the notion that sporadic and familial ALS are mechanistically related.
Chromogranin has been linked to mutant SOD1 by two previous studies. A frequently raised question is to what extent SOD1-based ALS mice are relevant in mimicking human disease. The association to chromogranin B in the SOD1 mouse model and now patient cohorts for both sporadic and familial ALS strongly supports the notion of converging cellular and molecular mechanisms of disease.
One important implication for scientists working on ALS is that the...