Elevated Plasma Phosphorylated Tau 181 in Amyotrophic Lateral Sclerosis

Area of Science:

• Neuroscience
• Biomarker Discovery
• Neurodegenerative Diseases

Background:

• Plasma phosphorylated tau (p-tau181) is a known biomarker for Alzheimer's disease (AD).
• Its role in other neurodegenerative conditions, like amyotrophic lateral sclerosis (ALS), is less understood.
• ALS typically lacks tau pathology, making p-tau181 elevation unexpected.

Purpose of the Study:

• To investigate the specificity of plasma p-tau181 in neurodegenerative diseases.
• To determine if plasma p-tau181 is elevated in ALS.
• To identify clinical correlates of elevated plasma p-tau181 in ALS patients.

Main Methods:

• Analyzed plasma p-tau181 levels in patients diagnosed with ALS (n=130), AD (n=79), and healthy controls (n=26).
• Used receiver operating characteristic (ROC) curves to assess the discrimination between AD and ALS.
• Correlated plasma p-tau181 levels with clinical signs (upper/lower motor neuron) and postmortem neuron loss in ALS patients.

Main Results:

• Plasma p-tau181 was significantly elevated in ALS patients compared to controls.
• Plasma p-tau181 showed poor discrimination between AD and ALS.
• Elevated plasma p-tau181 in ALS was associated with lower motor neuron (LMN) signs and spinal cord neuron loss.

Conclusions:

• Plasma p-tau181 is elevated in ALS, challenging the notion that it's exclusive to tauopathies.
• Elevated plasma p-tau181 may serve as a novel biomarker for LMN dysfunction in ALS.
• Further research is warranted to explore the mechanisms and clinical utility of p-tau181 in ALS.