Evaluation of the Braak hypothesis: how far can it explain the pathogenesis of Parkinson's disease?

Abstract

Braak’s proposal that, in patients with Parkinson’s disease, Lewy bodies and neurites progressively invade the brain through regions connected to autonomic and olfactory centers remains contentious. Confounding factors include the lack of an in vivo marker to examine the progression of Lewy pathology, the retrospective nature or absence of clinical information for many cross-sectional pathological datasets, and for those with limited disease (clinically or neuropathologically), the absence of information concerning additional conditions. Despite these data limitations at this time, the brain pathology for most patients with typical Parkinson’s disease can be predicted using Braak’s scheme. What this tells us about the pathogenesis of Parkinson’s disease will be explored in this review.

Keywords::

• α-synuclein
• Braak staging for PD
• clinicopathological correlations
• Lewy bodies
• Lewy neurites
• neuropathology
• Parkinson’s disease

Financial & competing interests disclosure

The authors have no conflicts of interest as detailed below and did not use any writing assistance. G Halliday is a Senior Principal Research Fellow of the National Health and Medical Research Council of Australia. The authors are employed by the academic institutions listed. There are no consultancies. G Halliday owns stock in Chochlear (2004–present) and NIB Holdings (2007–present). G Halliday has received travel expenses from the National Health & Medical Research Council of Australia (2010 & 2011 Research Fellowships Panels, 2011 Academy), International Conference on Alzheimer’s Disease (2010 organizing committee and meeting), Shanghai Movement Disorders Meeting (4/2010), NIH (4/2010 Workshop on Gaucher Disease & Parkinsonism), Elan Pharmaceuticals (4/2010 & 6/2011 San Francisco seminars and 9/2011 Tokyo Parkinson’s disease conference), World Parkinson’s Congress (2010), International Frontotemporal Dementia Conference (2010), International Society for Neurochamistry (2010 Asia Pacific Conference), International Synuclein Meeting (2010), International Movement Disorders Meeting (2011 organizing committee and meeting), NeuraSyn Summer School (2011) and WFN Congress on Parkinson’s disease and related disorders (2011). PCT Patent: Huang Y, Rowe D, Halliday G. Biomarkers for Parkinson’s disease. Pub. No.: WO/2009/039586. International Application No.: PCT/AU2008/001437 Publication Date:02.04.2009, International Filing Date:26.09.2008. Grants and other funding not associated with the project include the following. G Halliday is funded as a Chief Investigator by NHMRC project grants no. 510148 (2008–2010), no. 570850 (2009–2011), no. 1008307 (2011–2013), no. 1022325 (2011–2013) and no. 1029538 (2012–2014), ARC Linkage Infrastructure grant no. LE100100074 (2010), NHMRC strategic research funds & ARC joint ageing well, ageing productively program grant no. 401162 (2007–2011), the University of New South Wales Infrastructure grants (2010 & 2011) and Goldstar award (2010), Parkinson’s NSW (2011), and Michael J Fox Foundation and Shake-it-up Australia (2012). None of the author’s institution have contracts relating to this research. There are no agreements by the authors or their institutions involving a financial interest in this work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.