Predicting Cognitive Decline in PD from Alpha Synuclein in Cerebral Spinal Fluid



Predicting Cognitive Decline in PD from Alpha Synuclein in Cerebral Spinal Fluid

A new study being published in the April issue of the American Journal of Pathology has looked at data from 304 subjects from a study begun in 1987 that was one of the earliest studies that collected and catalogued specimens from early onset and newly diagnosed people with PARKINSON’S DISEASE and followed them for up to 8 years.  That study was the Deprenyl and Tocopherol Antioxidative Therapy of Parkinson’s (DATATOP) that found it possible to control symptoms and delay initiating treatment with levodopa by using Deprenyl.  It was a wide reaching study that led to a better understanding of the progression of the disease and the search to develop more neuroprotective therapies for PARKINSON’S DISEASE.

This new study was unique in that it drew on the data collected over a long period of time previously and did a new analysis of that information to find a connection to cognitive change or dementia related to levels of alpha synuclein found in samples of cerebral spinal fluid (CSF).  Levels of alpha synuclein in CSF were found to generally decrease as the disease progressed, but in some cases it was noted that higher levels of alpha synuclein were found in the CSF of subjects whose scores showed greater cognitive decline in the cognitive tests.  Subjects with more rapid cognitive also had relatively higher levels of alpha synuclein in their CSF.

The original study was divided into phases; Phase one was from entry into the study and Phase two started when the treatment with levodopa began.  All subjects enrolled in that study were in very early, untreated stages of PARKINSON’S DISEASE and without any symptoms of dementia. Cognitive testing was performed at entry and repeated every six months.  The United Parkinson’s Disease Rating Scale (UPDRS) cognitive testing section evaluated multiple aspects of cognition, including verbal learning, memory, visuospatial working memory and processing speed.  During Phase two cognitive changes became evident and were apparent across all sections of the cognitive testing. This data was carefully analyzed to control for age, sex, education, exposure to study drug and the actual dose of levodopa.

This research was done at the University of Washington (Seattle) School of Medicine, Department of Pathology under the direction of Jing Zhang, M.D., Ph.D.  First author is Tessandra Stewart, Ph.D.

“Cerebrospinal fluid alpha-synuclein predicts cognitive decline in Parkinson disease progression in the DATATOP cohort,” by Tessandra Stewart, Changqin Liu, Carmen Ginghina, Kevin C. Cain, Peggy Auinger, Brenna Cholerton, Min Shi, Jing Zhang, and the Parkinson Study Group DATATOP investigators (, The American Journal of Pathology, Volume 184, Issue 4 (April 2014)


Review by Marcia McCall

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