Tau positron emission tomography imaging in C9orf72 repeat expansion carriers

Area of Science:

• Neuroscience
• Neurology
• Radiology

Background:

• C9orf72 gene expansions are linked to neurodegenerative diseases.
• Tau pathology is a hallmark of several neurological disorders.
• Understanding tau accumulation in C9orf72 carriers is crucial for disease characterization.

Purpose of the Study:

• To assess tau accumulation in C9orf72 expansion carriers using positron emission tomography (PET).
• To investigate the relationship between tau PET imaging and clinical/biomarker data.
• To explore potential links between tau pathology and disease manifestation in C9orf72 carriers.

Main Methods:

• Positron emission tomography (PET) imaging with AV-1451 (flortaucipir) was conducted.
• Nine C9orf72 expansion carriers and 18 healthy controls underwent PET scans and psychometric evaluation.
• Regional AV-1451 standard uptake value ratios were analyzed and correlated with clinical and cerebrospinal fluid measures.

Main Results:

• C9orf72 expansion carriers demonstrated increased AV-1451 binding in the entorhinal cortex compared to controls.
• Postmortem analysis in one patient revealed primary age-related tauopathy.
• AV-1451 uptake did not correlate with clinical severity, disease duration, psychometric performance, or cerebrospinal fluid markers.

Conclusions:

• C9orf72 expansion carriers exhibit elevated AV-1451 uptake in the entorhinal cortex, indicating a potential for primary age-related tauopathy.
• Despite increased tau deposition, AV-1451 accumulation was not associated with psychometric performance in this cohort.