Our findings for neurological disorders were strikingly different from psychiatric disorders. In contrast to previous studies that either did not identify any cell type associations with Parkinson’s disease 61 or identified significant associations with cell types from the adaptive immune system 49, we found that cholinergic and monoaminergic neurons (which include dopaminergic neurons), enteric neurons and oligodendrocytes were significantly and independently associated with the disease. It is well established that loss of dopaminergic neurons in the substantia nigra is a hallmark of Parkinson’s disease. Our findings suggest that dopaminergic neuron loss in Parkinson’s disease is at least partly due to intrinsic biological mechanisms. In addition, other type of cholinergic and monoaminergic neurons are known to degenerate in Parkinson’s disease (e.g., raphe nucleus serotonergic neurons and cholinergic neurons of the pons), suggesting that specific pathological mechanisms may be shared across these neurons and lead to their degeneration. Two theories for the selective vulnerability of neuronal populations in Parkinson’s disease currently exist: the “spread Lewy pathology model” which assumes cell-to-cell contacts enabling spreading of prion-like α-synuclein aggregates 62; and the “threshold theory”
