Alimentary, my dear Watson? The challenges of enteric α-synuclein as a Parkinson's disease biomarker

被引:69
作者
Visanji, Naomi P. [1 ,2 ]
Marras, Connie [1 ,2 ]
Hazrati, Lili-Naz [3 ]
Liu, Louis W. C. [4 ]
Lang, Anthony E. [1 ,2 ]
机构
[1] Toronto Western Hosp, Morton & Gloria Shulman Movement Disorders Ctr, Toronto, ON M5T 2S8, Canada
[2] Toronto Western Hosp, Edmund J Safra Program Parkinsons Dis, Toronto, ON M5T 2S8, Canada
[3] Tanz Ctr Res Neurodegenerat Dis, Toronto, ON, Canada
[4] Toronto Western Hosp, Dept Med, Div Gastroenterol, Toronto, ON M5T 2S8, Canada
关键词
colon biopsy; alpha-synuclein; Parkinson's disease; biomarker; enteric nervous system; LEWY BODY DISEASE; MULTIPLE SYSTEM ATROPHY; NERVOUS-SYSTEM; COLONIC BIOPSIES; PATHOLOGY; BODIES; CONSTIPATION; INCLUSIONS; EXPRESSION; MEGACOLON;
D O I
10.1002/mds.25789
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
An accurate early diagnostic test for Parkinson's disease (PD) is a critical unmet need. Recently, independent groups using different histological techniques have reported that the presence of alpha-synuclein (alpha-syn) in colonic biopsy tissue is able to distinguish living patients with PD from those without the disease. In addition, a further study has suggested that the presence of alpha-syn in colonic biopsy tissue may be evident in early or even prodromal PD. However, several questions remain regarding the translation of these findings into using the assessment of alpha-syn deposition in the enteric nervous system as a diagnostic biomarker for prodromal PD. Here we address critical issues related to the location and quantification of enteric alpha-syn, detection of alpha-syn with currently available histological techniques, timing of detection of alpha-syn deposition, and, most crucially, whether enteric alpha-syn can distinguish those with PD from both healthy individuals and individuals with other related diseases. We conclude that, although enteric alpha-syn is a very exciting prospect, further studies will be vital to determine whether enteric alpha-syn deposition has the potential to be the biomarker for prodromal PD that the field so desperately seeks. (c) 2013 International Parkinson and Movement Disorder Society
引用
收藏
页码:444 / 450
页数:7
相关论文
共 44 条
[1]  
Adler CH, 2013, MOVEMENT DISORD, V28, pS314
[2]  
Aldakheel A, 2013, NEUROTHERAPEUTICS
[3]   Parkinson's disease is not associated with gastrointestinal myenteric ganglion neuron loss [J].
Annerino, Dana M. ;
Arshad, Shawn ;
Taylor, Georgia M. ;
Adler, Charles H. ;
Beach, Thomas G. ;
Greene, James G. .
ACTA NEUROPATHOLOGICA, 2012, 124 (05) :665-680
[4]   Multi-organ distribution of phosphorylated α-synuclein histopathology in subjects with Lewy body disorders [J].
Beach, Thomas G. ;
Adler, Charles H. ;
Sue, Lucia I. ;
Vedders, Linda ;
Lue, LihFen ;
White, Charles L., III ;
Akiyama, Haru ;
Caviness, John N. ;
Shill, Holly A. ;
Sabbagh, Marwan N. ;
Walker, Douglas G. .
ACTA NEUROPATHOLOGICA, 2010, 119 (06) :689-702
[5]   Expression pattern and localization of alpha-synuclein in the human enteric nervous system [J].
Boettner, Martina ;
Zorenkov, Dimitri ;
Hellwig, Ines ;
Barrenschee, Martina ;
Harde, Jonas ;
Fricke, Tobias ;
Deuschl, Guenther ;
Egberts, Jan-Hendrik ;
Becker, Thomas ;
Fritscher-Ravens, Annette ;
Arlt, Alexander ;
Wedel, Thilo .
NEUROBIOLOGY OF DISEASE, 2012, 48 (03) :474-480
[6]   Insights into REM sleep behavior disorder pathophysiology in brainstem-predominant Lewy body disease [J].
Boeve, B. F. ;
Dickson, D. W. ;
Olson, E. J. ;
Shepard, J. W. ;
Silber, M. H. ;
Ferman, T. J. ;
Ahlskog, J. E. ;
Benarroch, E. E. .
SLEEP MEDICINE, 2007, 8 (01) :60-64
[7]   Gastric α-synuclein immunoreactive inclusions in Meissner's and Auerbach's plexuses in cases staged for Parkinson's disease-related brain pathology [J].
Braak, H ;
de Vos, RAI ;
Bohl, J ;
Del Tredici, K .
NEUROSCIENCE LETTERS, 2006, 396 (01) :67-72
[8]   Stages in the development of Parkinson's disease-related pathology [J].
Braak, H ;
Ghebremedhin, E ;
Rüb, U ;
Bratzke, H ;
Del Tredici, K .
CELL AND TISSUE RESEARCH, 2004, 318 (01) :121-134
[9]   Invited Article: Nervous system pathology in sporadic Parkinson disease [J].
Braak, Heiko ;
Del Tredici, Kelly .
NEUROLOGY, 2008, 70 (20) :1916-1925
[10]   Parkinson's disease: lesions in dorsal horn layer I, involvement of parasympathetic and sympathetic pre- and postganglionic neurons [J].
Braak, Heiko ;
Sastre, Magdalena ;
Bohl, Juergen R. E. ;
de Vos, Rob A. I. ;
Del Tredici, Kelly .
ACTA NEUROPATHOLOGICA, 2007, 113 (04) :421-429