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Reduced Levels of Two Proteins May Signal Early Parkinsonís

Some people with a genetic mutation that predisposes them to Parkinson’s disease (PD) have reduced levels of certain proteins in their cerebrospinal fluid, according to a study published online December 14 in the journal Neurology.  Additionally, levels of these proteins are associated with the activity of dopamine in the brain, suggesting that they might be helpful in diagnosing Parkinson’s in its early stages.

The two proteins, amyloid β and tau, are best known for their involvement in Alzheimer’s disease, where they may be harmful to the brain.  However, increasing evidence also links the two proteins to Parkinson’s.  Scientists have detected amyloid β and tau in Lewy bodies, the clumps of proteins that form in the brains of people with Parkinson’s.  Also, some studies of people living with the sporadic (non-genetic) form of Parkinson’s have reported lower-than-normal levels of amyloid β and tau in cerebrospinal fluid (CSF), the fluid that bathes and cushions the spinal cord and brain.  But scientists don’t yet understand the roles of these proteins, if any, in Parkinson’s.

So researchers led by Jing Zhang, M.D., Ph.D., at the University of Washington School of Medicine investigated the proteins.  They studied levels of amyloid β and tau in the CSF of people carrying mutations in the leucine-rich repeat kinase 2 (LRRK2) gene.  Mutations in LRRK2 can increase a person’s chances of developing Parkinson’s and sometimes cause the disease.

The researchers compared the levels of the two proteins in CSF from 18 people who carry LRRK2 mutations but had no Parkinson’s symptoms (asymptomatic carriers) and eight people with symptoms resembling sporadic Parkinson’s (symptomatic carriers).  The researchers collected CSF samples with a spinal tap, a procedure in which doctors insert a needle between vertebrae in the lower back and extract a small amount of fluid much like a blood draw.  Study participants also underwent multiple positron emission tomography (PET) scans of the brain to determine whether their brains showed reduced activity of the neurons which make and process dopamine, a common characteristic of Parkinson’s.


  • People carrying the LRRK2 mutation, who also showed signs of Parkinson’s, had slightly lower CSF levels of amyloidβ and tau than people without any Parkinson’s symptoms.
  • Across the entire study group, PET scan showed that CSF levels of amyloid β were associated with dopamine activity.  In other words, people with relatively low CSF levels of amyloid β had reduced levels of dopamine activity, whereas those with higher levels of amyloid β in their CSF tended to show better dopamine neuron activity, similar to a person without Parkinson’s.
  • Among people with a particular LRRK2 mutation known as G2019S, both amyloid β and tau CSF levels associated with dopamine function.

What Does It Mean?

The long-term goal of many Parkinson’s researchers is not only to find a cure, but also to find a way to prevent the disease, just as vaccines are used to prevent infections.  However, in order to find such an intervention, researchers need to first identify people who are at an increased risk for Parkinson’s, and then explore interventions that may prevent the disease in those people.

Here, the researchers took the novel approach of using a genetic marker to identify people at risk for Parkinson’s.  First, they identified people with genetic mutations in the LRRK2 gene.  These individuals have about a 30 percent chance of developing Parkinson’s by their 60s.  Because most participants had not yet developed PD, researchers then used sophisticated brain imaging to see if spinal fluid analysis may serve as a potential way to identify which of these people may be at a even higher risk for Parkinson’s.

The findings highlight the fact that spinal fluid, obtained by a spinal tap, may one day be a useful tool for risk assessment of people who are at increased risk for Parkinson’s.  More studies are required to confirm that these findings may be applicable to people at risk for Parkinson’s without LRRK2 mutations.

The study also supports a connection between Alzheimer’s disease and Parkinson’s pathology. Further research is needed to determine whether decreased amyloid β and tau levels in CSF arise from increased deposition of the proteins in the brains of people with PD.

Reference: Aasly JO, Shi M, Sossi V, Stewart T, Johansen KK, Wszolek ZK, Uitti RJ, Hasegawa K, Yokoyama T, Zabetian CP, Kim HM, Leverenz JB, Ginghina C, Armaly J, Edwards KL, Snapinn KW, Stoessl AJ, Zhang J. Cerebrospinal fluid amyloid β and tau in LRRK2 mutation carriers. Neurology 2012 Jan.;78(1):55–61.

Source Date: Jan 31 2012