Our present findings of (1) enhanced pS129 asyn (particularly in DA-expressing neurons) in the hypothalamus (Fig. 2a,b), (2) an apparent shift to more insoluble pS129 in the hippocampus (Fig. 2a,c, S5j), (3) decreased CRF expression in both regions (Fig. 1b, 5a), (4) decreased baseline plasma CORT (Fig. 1c) and (5) adrenal gland atrophy (Fig. 1d), indicate multi-level HPA axis dysfunction, including partial adrenal insufficiency associated with asyn-dependent PD pathology. This evidence concerns the gene CRH and Parkinson disease.