Effect of age on brain metabotropic glutamate receptor subtype 5 measured with [¹⁸F]FPEB PET

Metabotropic glutamate receptor subtype 5 (mGluR5) is integral to the brain glutamatergic system and cognitive function. This study investigated whether aging is associated with decreased brain mGluR5 availability.

Cognitively normal participants (n = 45), aged 18 to 84 years, underwent [¹⁸F]FPEB positron emission tomography scans to quantify brain mGluR5. Distribution volume (V_T) was computed using a venous or arterial input function and equilibrium modeling from 90 to 120 min. In the primary analysis, the association between age and V_T in the hippocampus and association cortex was evaluated using a linear mixed model. Exploratory analyses assessed the association between age and V_T in multiple brain regions. The contribution of gray matter tissue alterations and partial volume effects to associations with age was also examined.

In the primary analysis, older age was associated with lower [¹⁸F]FPEB binding to mGluR5 (P = 0.026), whereas this association was not significant after gray matter masking or partial volume correction to account for age-related tissue loss. Post hoc analyses revealed an age-related decline in mGluR5 availability in the hippocampus of 4.5% per decade (P = 0.007) and a non-significant trend in the association cortex (P = 0.085). An exploratory analysis of multiple brain regions revealed broader inverse associations of age with mGluR5 availability, but not after partial volume correction.

Reductions in mGluR5 availability with age appear to be largely mediated by tissue loss. Quantification of [¹⁸F]FPEB binding to mGluR5 may expand our understanding of age-related molecular changes and the relationship with brain tissue loss.