[11C]-WAY100635 PET demonstrates marked 5-HT1A receptor changes in sporadic ALS

Area of Science:

• Neuroscience
• Neurology
• Radiology

Background:

• Amyotrophic lateral sclerosis (ALS) pathogenesis involves neuronal loss beyond the motor cortex, even without dementia.
• Assessing in vivo cortical involvement in ALS remains challenging.
• The 5-hydroxytryptamine (5-HT1A) receptor is expressed on cortical pyramidal neurons.

Purpose of the Study:

• To evaluate [11C]-WAY100635 Positron Emission Tomography (PET) as a marker for cerebral neuronal loss or dysfunction in ALS.
• To quantify cortical 5-HT1A receptor binding potential (BP) in ALS patients compared to healthy controls.

Main Methods:

• Twenty-one ALS subjects and 19 healthy volunteers underwent [11C]-WAY100635 PET brain imaging.
• A cortical template was used to measure regional [11C]-WAY100635 binding potential (BP) reductions in ALS patients.
• Statistical Parametric Mapping (SPM) identified specific cortical regions with significant binding decreases.

Main Results:

• ALS patients showed a significant 21% reduction in global cortical and raphe [11C]-WAY100635 BP (P < 0.001).
• Regional VOI analysis revealed decreases ranging from 16% to 29%, with greater reductions in those with bulbar involvement.
• SPM analysis highlighted the greatest differences in frontotemporal regions, cingulate, and lateral precentral gyri.

Conclusions:

• Reduced cortical [11C]-WAY100635 binding in ALS patients likely reflects neuronal loss or damage affecting 5-HT1A receptors.
• These findings suggest [11C]-WAY100635 PET may serve as a potential in vivo biomarker for cortical dysfunction in ALS.
• Further research is warranted to explore the role of the 5-HT1A receptor in ALS pathogenesis and the utility of this PET tracer.