HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Correspondence: Submit a response Alert me when this article is cited Alert me when Correspondence are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Minguez-Castellanos, A. Articles by Munoz, D. G. Search for Related Content PubMed PubMed Citation Articles by Minguez-Castellanos, A. Articles by Munoz, D. G. Related Collections Autonomic diseases Parkinson's disease/Parkinsonism Dementia with Lewy bodies Cohort studies

Do -synuclein aggregates in autonomic plexuses predate Lewy body disorders?

A cohort study

From the Departments of Neurology (A.M.-C., F.E.-S., A.O.-M.), Pathology and Tumor and Tissue Bank (C.E.C., A.C.), and Nuclear Medicine (A.C.R., M.G.-R.), Virgen de las Nieves University Hospital, Granada, and Tissue Bank for Neurological Research (D.G.M.), Madrid, Spain; and St. Michael's Hospital (D.G.M.), University of Toronto, Ontario, Canada.

Address correspondence and reprint requests to Dr. A. Mínguez-Castellanos, Servicio de Neurología, Hospital Universitario Virgen de las Nieves, CRT 3ª planta, Carretera de Jaén s/n, 18013 Granada, Spain aminguezc{at}meditex.es

Objective: To determine the prevalence of -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 [¹²³I]metaiodobenzylguanidine uptake was reduced in the AS+ group (p = 0.03). Striatal [¹²³I]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 -synuclein aggregates in peripheral autonomic neurons may represent an early presymptomatic phase in the development of Lewy body disorders.

*These authors contributed equally to this work.

Supported by grants from "Fundacion Virgen de las Nieves," "Consejeria de Salud" of the Andalusian Government (189/02), and "Instituto Carlos III" of the Spanish Government (FIS 0310/03; Red CIEN C03/06).

Disclosure: The authors report no conflicts of interest.

Received May 31, 2006. Accepted in final form February 5, 2007.

This article has been cited by other articles:

				M. A. Mena and J. Garcia de Yebenes Glial Cells as Players in Parkinsonism: The "Good," the "Bad," and the "Mysterious" Glia Neuroscientist, December 1, 2008; 14(6): 544 - 560. [Abstract] [PDF]

				H. Braak and K. Del Tredici Invited Article: Nervous system pathology in sporadic Parkinson disease Neurology, May 13, 2008; 70(20): 1916 - 1925. [Full Text] [PDF]

				S. Orimo, T. Uchihara, A. Nakamura, F. Mori, A. Kakita, K. Wakabayashi, and H. Takahashi Axonal {alpha}-synuclein aggregates herald centripetal degeneration of cardiac sympathetic nerve in Parkinson's disease Brain, March 1, 2008; 131(3): 642 - 650. [Abstract] [Full Text] [PDF]