Pathological alpha-synuclein in gastrointestinal tissues from prodromal parkinson's disease patients

Important result this... I haven't seen the paper in full yet but conformation of staining in the past appeared just as important as whether there is any staining or not... previous studies have found a high proportion of controls also stain positive. Particularly interesting here is that a significant proportion of patients had alpha synuclein prior to diagnosis!!

Ann Neurol. 2016 Mar 26. doi: 10.1002/ana.24648. [Epub ahead of print]

Stokholm MG, Danielsen EH, Hamilton-Dutoit SJ, Borghammer P.

http://onlinelibrary.wiley.com/doi/10.1002/ana.24648/abstract

OBJECTIVE:

It has been hypothesized that Lewy pathology initiates in the enteric nervous system years prior to debut of clinical motor symptoms in Parkinson's disease patients. This study investigates whether Lewy pathology is present in various gastrointestinal tract tissues from Parkinson's disease patients in the prodromal phase.

METHODS:

We used the Danish National Pathology Registry, to identify archived paraffin embedded tissue blocks from 57 Parkinson's disease patients (98 blocks) and 90 control subjects (98 blocks). We employed two different immunohistochemistry techniques visualizing aggregated α -synuclein and phosphorylated α -synuclein.

RESULTS:

Thirty-nine Parkinson's disease patients contributed tissues obtained in the prodromal disease phase, whilst 18 Parkinson's disease patients contributed tissues obtained solely after Parkinson's diagnosis. Prodromal tissues were obtained on average 7.0 years prior to diagnosis (range: 20 years - 4 months), and post-diagnosis tissue on average 2.8 years after diagnosis (range: 2 days - 18 years). Phosphorylated- α -synuclein positivity was seen in 22/39 (56%) prodromal Parkinson's disease subjects and 30/67 (45%) prodromal tissue blocks. These fractions were significantly higher compared to control subjects (p=0.0001 and p=0.0032, respectively). In contrast, no significant difference was seen in the positivity rate between prodromal Parkinson's disease patients and controls when using the aggregated α -synuclein immunohistochemistry technique.

INTERPRETATION:

We detected Lewy pathology in the gastrointestinal tract of patients up to 20 years prior to their Parkinson's disease diagnosis. These findings are in accordance with a hypothesized prodromal disease phase spanning 10-20 years.