Do alpha-synuclein aggregates in autonomic plexuses predate Lewy body disorders?: a cohort study

Abstract

Objective: To determine the prevalence of alpha-synuclein (AS) aggregates in abdominopelvic autonomic plexuses in the general population and to evaluate the relationship between this finding and the subsequent development of neurologic dysfunction.

Methods: First, surgical specimens from 100 patients (ages 44 to 84) undergoing a wide resection of an abdominopelvic organ were examined by anti-AS immunostaining. Second, 16 patients (6 AS+ and 10 randomly selected AS-) participated in yearly double-blinded neurologic assessments.

Results: AS aggregates were found in autonomic plexuses in 9% of the whole sample (95% CI 3.4 to 14.6%) but were more common in vesicoprostatic (26%) than in digestive tract (4%) specimens. At 16 months after the biopsy, no prevalent cases of Parkinson disease, dementia, or autonomic failure were diagnosed among participants. One AS+ patient had previously been diagnosed with REM sleep behavior disorder. Seven of 10 control subjects but none of the 6 AS+ patients had a diagnosis of hypertension (p = 0.01). During phase IV of Valsalva maneuver, AS+ group exhibited a longer blood pressure recovery time (p = 0.03), with one patient showing absence of blood pressure overshoot. Cardiac [(123)I]metaiodobenzylguanidine uptake was reduced in the AS+ group (p = 0.03). Striatal [(123)I]ioflupane uptake was abnormally low in only one AS+ patient. At 30 months after the biopsy, lower cardiac and striatal uptake values tended to correlate with higher Unified Parkinson's Disease Rating Scale III scores (p = 0.07).

Conclusion: The common presence of alpha-synuclein aggregates in peripheral autonomic neurons may represent an early presymptomatic phase in the development of Lewy body disorders.