Alpha-synuclein exhibits a dramatic redistribution within the neuronal compartment as a function of aging: the best-validated primary risk factor for PD. A quantitative morphological postmortem analysis of α-syn immunoreactivity within SN DA neurons of humans reveals a distinct pattern of increased staining within neuronal soma with advancing chronological age (Chu and Kordower, 2007). Samples were from individuals with a mean age of 31 years (young group, N = 6), 55 years (middle-aged, N = 4) and 84 years (aged, N = 8). Alpha-synuclein immunoreactivity was rarely detected in the soma of SN neurons in young individuals and was restricted to its normal location in the neuropil. With advancing age, a progressive increase in somatic immunoreactivity was observed, culminating in a 639% increase in aged subjects. Quantitation of the intensity of somatic staining on a per neuron basis confirmed this pattern, illustrating a mean 57% increase in aged subjects as compared to young. It is noteworthy that none of these samples exhibited α-syn aggregates, suggesting that this intracellular redistribution of α-syn may be an ongoing aging-related event that precedes processes of aggregation. The same pattern was observed in aging monkeys. Of importance to the loss-of-function hypothesis, no comparison to α-syn distribution/levels in striatum was performed, providing no opportunity to assess whether increased somatic levels are associated with decreased synaptic levels.