GM1 ganglioside in Parkinson\u27s disease: Pilot study of effects on dopamine transporter binding.

OBJECTIVE: GM1 ganglioside has been suggested as a treatment for Parkinson\u27s disease (PD), potentially having symptomatic and disease modifying effects. The current pilot imaging study was performed to examine effects of GM1 on dopamine transporter binding, as a surrogate measure of disease progression, studied longitudinally. METHODS: Positron emission tomography (PET) imaging data were obtained from a subset of subjects enrolled in a delayed start clinical trial of GM1 in PD [1]: 15 Early-start (ES) subjects, 14 Delayed-start (DS) subjects, and 11 Comparison (standard-of-care) subjects. Treatment subjects were studied over a 2.5 year period while Comparison subjects were studied over 2 years. Dynamic PET scans were performed over 90 min following injection of [(11)C]methylphenidate. Regional values of binding potential (BPND) were analyzed for several striatal volumes of interest. RESULTS: Clinical results for this subset of subjects were similar to those previously reported for the larger study group. ES subjects showed early symptomatic improvement and slow symptom progression over the study period. DS and Comparison subjects were initially on the same symptom progression trajectory but diverged once DS subjects received GM1 treatment. Imaging results showed significant slowing of BPND loss in several striatal regions in GM1-treated subjects and in some cases, an increased BPND in some striatal regions was detected after GM1 use. INTERPRETATION: Results of this pilot imaging study provide additional data to suggest a potential disease modifying effect of GM1 on PD. These results need to be confirmed in a larger number of subjects

Alpha-synuclein cortical Lewy bodies correlate with dementia in Parkinson's disease

Background: Dementia is a frequent complication of idiopathic parkinsonism or PD, usually occurring later in the protracted course of the illness. The primary site of neuropathologic change in PD is the substantia nigra, but the neuropathologic and molecular basis of dementia in PD is less clear. Although Alzheimer’s pathology has been a frequent finding, recent advances in immunostaining of α-synuclein have suggested the possible importance of cortical Lewy bodies (CLBs) in the brains of demented patients with PD.Methods: The brains of 22 demented and 20 nondemented patients with a clinical and neuropathologic diagnosis of PD were evaluated with standard neuropathologic techniques. In addition, CLBs and dystrophic neurites were identified immunohistochemically with antibodies specific for α-synuclein and ubiquitin; plaques and tangles were identified by staining with thioflavine S. Associations between dementia status and pathologic markers were tested with logistic regression.Results: CLBs positive for α-synuclein are highly sensitive (91%) and specific (90%) neuropathologic markers of dementia in PD and slightly more sensitive than ubiquitin-positive CLBs. They are better indicators of dementia than neurofibrillary tangles, amyloid plaques, or dystrophic neurites.Conclusion: CLBs detected by α-synuclein antibodies in patients with PD are a more sensitive and specific correlate of dementia than the presence of Alzheimer’s pathology, which was present in a minority of the cases in this series.</jats:p