Do people carrying a Parkinson's risk mutation show brain inflammation even without Parkinson's disease?

Details

Glucocerebrosidase gene mutations are a common genetic risk factor for Parkinson's disease. They have incomplete penetrance: not every carrier develops the disease. This study aimed to compare microglial activation and dopamine integrity in mutation carriers without Parkinson's disease with controls.

In an observational PET imaging comparison, researchers scanned 9 glucocerebrosidase gene mutation carriers without Parkinson's disease and 29 age-matched controls. They measured microglial activation using 11C-(R)-PK11195 binding potentials and dopamine terminal integrity using 18F-dopa influx constants.

The carriers had increased 11C-(R)-PK11195 binding potential in the substantia nigra compared with controls (Student t test; right, t = −4.45, P = 0.0001). Statistical parametric mapping also identified significantly increased binding potential in the occipital and temporal lobes, cerebellum, hippocampus, and mesencephalon.

The degree of hyposmia, or reduced sense of smell, correlated with regional 11C-(R)-PK11195 binding potentials in the substantia nigra (Spearman's rank, P = 0.0066). Mean striatal 18F-dopa uptake was similar to healthy controls.

The authors concluded that in vivo 11C-(R)-PK11195 PET imaging detects neuroinflammation in brain regions susceptible to Lewy pathology in glucocerebrosidase gene mutation carriers without Parkinson's disease.

The abstract carries a © 2020 The Authors notice. Movement Disorders was published by Wiley Periodicals LLC on behalf of the International Parkinson and Movement Disorder Society.