Sunday Aug 14, 2022
Sunday Aug 14, 2022

Study finds new insights about tau protein in ALS patients

2021 Nov 30, 12:35, Boston
Representative image (photo via ANI)

A team of researchers at the Massachusetts General Hospital have found that people suffering from amyotrophic lateral sclerosis or ALS who carry a mutation in the C9orf72 gene, exhibit elevated levels of tau and phosphorylated tau protein in their motor cortex region of the brain.

The study was published in the 'Brain Pathology Journal'.

It also identified new genetic mutations in the tau gene and revealed that the ratio of different forms of tau protein may be an indicator of disease progression in ALS.

"This study focused on tau, a protein that is critical for stabilizing the structure of nerve cells and has been implicated in Alzheimer's disease, and whether it plays a role in ALS pathogenesis as it can form aggregates and lead to cellular dysfunction in a number of neurodegenerative disorders," said senior author Ghazaleh Sadri-Vakili, PhD, director of the NeuroEpigenetics Laboratory at the MassGeneral Institute for Neurodegenerative Disease and the Sean M. Healey and AMG Center for ALS at Mass General.

Using post-mortem brain samples from people with ALS, the researchers discovered that tau and one of its phosphorylated forms are increased in the brains of patients whose cells carry a mutation in the C9orf72 gene that was linked to ALS and dementia 10 years ago.

"We also identified new genetic mutations in the tau gene that is specific to ALS and may have functional consequences that may exacerbate disease onset or progression," said Sadri-Vakili.

To determine if tau protein is a viable biomarker for ALS, the team measured tau and its phosphorylated form in cerebrospinal fluid from people living with ALS. The investigators demonstrated that increases in these particular forms of tau protein in patients' cerebrospinal fluid correlated with disease progression. Therefore, tau levels -- and specifically the ratio between tau and the phosphorylated form of the tau protein -- might help clinicians predict patients' rate of disease progression.

"These findings are exciting as there is an unmet and urgent need for disease biomarkers in ALS," noted Sadri-Vakili.

Funding was provided by the Judith and Jean Pape Adams Charitable Foundation, the Byrne Family Endowed Fellowship in ALS Research, the Alzheimer's Association, the Jack Satter Foundation, and the National Institute on Aging

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