Genetic Overlap Between Some Types of ALS and and Dementia Interview with:

Celeste Karch, PhD Assistant Professor of Psychiatry Molecular mechanisms underlying tauopathies Washington University School of Medicine St Louis

Dr. Karch

Celeste Karch, PhD
Assistant Professor of Psychiatry
Molecular mechanisms underlying tauopathies
Washington University School of Medicine
St Louis What is the background for this study? What are the main findings?

Response: Nearly half of all patients with amyotrophic lateral sclerosis (ALS), a fatal neuromuscular disorder, develop cognitive problems that affect memory and thinking. Why a disease that primarily affects movement also disrupts thinking has been unclear.

Our findings suggest that genetic connections between the two disorders may explain why they share some of the same features and suggest that some drugs developed to treat ALS also may work against frontotemporal dementia and vice versa. We used a statistical method in almost 125,000 individuals with ALS, frontotemporal dementia (FTD), progressive supranuclear palsy, corticobasal degeneration, Alzheimer’s disease and Parkinson’s disease to determine whether there are common genetic variants that increase risk for multiple neurodegenerative diseases.

We found that common variants near the MAPT gene, which makes the tau protein, increases risk for ALS. MAPT has previously had been associated with diseases including frontotemporal dementia and Alzheimer’s disease. But the gene hadn’t been linked to ALS. We also identified variations in a second gene, BNIP1, which normally plays an important role in protecting against cell death, increased the risk of both ALS and frontotemporal dementia. ImportantlyBNIP1 mRNA levels were altered in people who had ALS and in patients with frontotemporal dementia, suggesting the BNIP1 may be a potential therapeutic target for both disorders. What should readers take away from your report? 

Response: Leveraging large datasets across neurodegenerative disorders can reveal new disease risk factors that wouldn’t be obvious in smaller studies What recommendations do you have for future research as a result of this work? 

Response: We still need to understand what role common variants in MAPT or the tau protein itself play in ALS. Beyond MAPT and BNIP1, we found a number of variants that increase risk for ALS and FTD; so, more work needs to be done to understand the functional impact of the variants and the role of these genes in disease.


Karch CM, Wen N, Fan CC, et al. Selective Genetic Overlap Between Amyotrophic Lateral Sclerosis and Diseases of the Frontotemporal Dementia Spectrum. JAMA Neurol. Published online April 09, 2018. doi:10.1001/jamaneurol.2018.0372

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Last Updated on April 9, 2018 by Marie Benz MD FAAD