Poorer aging trajectories are associated with elevated serotonin synthesis capacity

Area of Science:

• Neuroscience
• Radiochemistry
• Gerontology

Background:

• The dorsal raphe nucleus (DRN) is crucial for brain serotonin and an early target in Alzheimer's disease (AD).
• Aging impacts serotonin systems and is associated with neurodegenerative changes and mood disorders.

Purpose of the Study:

• To measure serotonin synthesis capacity in the DRN using [18F]Fluoro-m-tyrosine ([18F]FMT) PET in healthy adults across the lifespan.
• To investigate the relationship between DRN serotonin synthesis capacity and aging-related structural brain changes, depression symptoms, and AD pathology.

Main Methods:

• 111 healthy adults (18-85 years) underwent [18F]FMT PET to quantify DRN serotonin synthesis capacity (Ki).
• Correlations were examined between DRN [18F]FMT Ki and longitudinal MRI (cortical thickness), depression scores, and cross-sectional tau ([18F]Flortaucipir) and amyloid-beta ([11C]PiB) PET.
• Exploratory analyses considered sex differences.

Main Results:

• Serotonin synthesis capacity in the DRN was elevated in older adults compared to younger adults.
• Higher DRN [18F]FMT Ki correlated with greater temporal lobe cortical atrophy and increased longitudinal depression symptoms, particularly in older adults.
• No direct associations were found between DRN serotonin synthesis capacity and AD tau or amyloid-beta pathology.
• Older adult females with the highest serotonin synthesis capacity showed the strongest link between entorhinal cortex tau and depression.

Conclusions:

• Elevated DRN serotonin synthesis capacity, measured by [18F]FMT PET, may serve as a biomarker for accelerated brain aging.
• This finding highlights the interplay between serotonin system changes, structural brain alterations, and affective well-being in aging.
• PET imaging of the serotonin system offers a promising avenue for understanding aging trajectories relevant to AD and mood disorders.