Study Rationale:
Alpha-synuclein aggregation in the brain is the main pathology of Parkinson’s disease (PD). Cerebrospinal fluid (CSF) levels of alpha-synuclein are lower in PD. It is not clear if alpha-synuclein levels are also low in CSF of people with both Alzheimer’s disease (AD) and PD pathology. To answer this question, we need to use CSF samples from individuals who have undergone autopsy. However, we do not know how CSF levels of proteins and lipids are affected by the death process. This pilot study will examine the correlation between CSF levels (collected before and after death) of alpha-synuclein, amyloid-beta, tau and sphingolipids, which are all biomarkers of interest for PD.
Hypothesis:
We hypothesize that CSF levels of alpha-synuclein, amyloid-beta, tau and sphingolipids collected before death will correlate to those collected after death.
Study Design:
We will compare CSF levels collected both before and after death from stored samples of 15 individuals with various pathological diagnoses. Diagnoses include normal pathological aging, progressive supranuclear palsy, AD and Lewy body dementia. The average post-mortem autopsy interval is 13.9 hours (range 1.8-26.6).
Impact on Diagnosis/Treatment of Parkinson’s Disease:
This pilot study is the first step in determining whether CSF alpha-synuclein, amyloid-beta, tau and lipid measures differ in persons with both AD and PD pathology compared to PD pathology alone. This information will be important in developing a diagnostic biomarker for PD pathology and for identifying patients who will most benefit from specific drugs.
Next Steps for Development:
If we find good correlations between pre- and post-mortem levels of alpha-synuclein, amyloid-beta, tau and sphingolipids, our next step will be to examine these markers in post-mortem CSF of 34 individuals with Lewy body pathology only, 65 people with both AD and Lewy Body pathology, and 44 with pathological aging changes.