Pattern of cortical thinning associated with the BDNF Val66Met polymorphism in Parkinson’s disease

Abstract

The brain-derived neurotrophic factor (BDNF) val66met polymorphism has been suggested to modulate cognitive deterioration in Parkinson s disease (PD). In particular, the val/val genotype has been recently suggested to increase the risk of cognitive decline in this population. However, to date, little is known about the underlying brain alterations responsible for this association. Here, in a cohort of 93 early PD patients with preserved cognition from the Parkinson s Progression Markers Initiative (PPMI), we found that BDNF val/val patients experience an increased cortical atrophy rate with respect to met carriers in frontal and posterior-cortical regions (p<0.05, corrected). Additionally, BDNF val/val PD patients showed lower I123-ioflupane SPECT DAT uptake in the contralateral caudate region (p=0.017) than met carriers, suggesting an increased striatal dopaminergic degeneration, which represents the pathological hallmark of PD. None of these observations were found in a sample of 38 healthy control (HC) subjects of comparable age and gender. We also observed an interaction effect on brain structure between the BDNF and APOE genotypes: cortical atrophy was associated with harboring the apoliprotein E (APOE) ε4 allele only in BDNF val/met subjects (both in HC and PD groups). Overall, these findings suggest that harboring the BDNF val/val genotype in PD leads to a set of cortical and subcortical brain alterations that could promote cognitive decline in this population.