Researchers discover new insights about tau proteins in people living
with ALS

Date:
November 15, 2021
Source:
Massachusetts General Hospital
Summary:
Investigators found elevated levels of tau and a phosphorylated
form of the tau protein in brain tissue from deceased people who
had amyotrophic lateral sclerosis (ALS) and carried a mutation in
the C9orf72 gene. The team also identified new genetic mutations in
the tau gene that may exacerbate ALS onset or progression. Tau in
the cerebrospinal fluid may be a viable biomarker for ALS because
levels correlate with disease progression.



FULL STORY ==========================================================================
A team led by investigators at Massachusetts General Hospital (MGH)
has shown that people living with amyotrophic lateral sclerosis (ALS),
or Lou Gehrig's disease, who carry a mutation in the C9orf72 gene
exhibit elevated levels of tau and phosphorylated tau protein in the
motor cortex region of the brain. The research, which is published in
Brain Pathology, 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," says 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 are specific to ALS and may have functional consequences that may exacerbate disease onset or progression,"
says 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," notes Sadri-Vakili.

Co-authors include Tiziana Petrozziello, Ana C. Amaral, Simon Dujardin,
Sali M.K. Farhan, James Chan, Bianca A. Trombetta, Pia Kivisa"kk,
Alexandra N.

Mills, Evan A. Bordt, Spencer E. Kim, Patrick M. Dooley, Caitlin Commins, Theresa R. Connors, Derek H. Oakley, Anubrata Ghosal, Teresa Gomez-Isla, Bradley T. Hyman, Steven E. Arnold, Tara Spires-Jones, Merit E. Cudkowicz,
and James D. Berry.

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.

========================================================================== Story Source: Materials provided by Massachusetts_General_Hospital. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Tiziana Petrozziello, Ana C. Amaral, Simon Dujardin, Sali
M. K. Farhan,
James Chan, Bianca A. Trombetta, Pia Kivisa"kk, Alexandra N. Mills,
Evan A. Bordt, Spencer E. Kim, Patrick M. Dooley, Caitlin Commins,
Theresa R.

Connors, Derek H. Oakley, Anubrata Ghosal, Teresa Gomez‐Isla,
Bradley T. Hyman, Steven E. Arnold, Tara Spires‐Jones,
Merit E.

Cudkowicz, James D. Berry, Ghazaleh Sadri‐Vakili. Novel
genetic variants in MAPT and alterations in tau phosphorylation
in amyotrophic lateral sclerosis post‐mortem motor cortex
and cerebrospinal fluid.

Brain Pathology, 2021; DOI: 10.1111/bpa.13035 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/11/211115123558.htm

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