GFAP protein levels may help predict dementia risk in Parkinson’s

Blood levels increased in patients with cognitive impairment: Study

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Levels of the GFAP protein in blood are significantly higher in Parkinson’s disease patients with cognitive impairment — particularly those with dementia — compared with healthy people, a new study shows.

According to researchers, blood GFAP levels could accurately identify Parkinson’s patients with mild cognitive impairment (MCI) who ended up developing dementia.

Thus, the findings suggest that these levels “might have prognostic value for predicting MCI-to-dementia conversion in PD [Parkinson’s disease],” the team wrote.

The study, “Plasma GFAP in Parkinson’s disease with cognitive impairment and its potential to predict conversion to dementia,” was published in npj Parkinson’s Disease.

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Cognitive impairment is a common non-motor symptom of Parkinson’s disease. Up to 40% of patients are estimated to develop dementia, or memory and thinking difficulties that limit a person’s ability to function independently in day-to-day life.

As such, identifying predictive markers of dementia is clinically relevant to inform monitoring and treatment decisions.

GFAP, or glial fibrillary acidic protein, is a structural protein found in astrocytes, star-shaped cells in the nervous system that help to support the function of neurons. It has been proposed as a biomarker of reactive astrogliosis — an increase in astrocytes in response to neuronal damage that has been linked to debilitative effects in Parkinson’s.

But “whether GFAP can be used as a potential biomarker to predict cognitive progression of PD is unknown,” the researchers wrote.

To address this, a team of scientists at Fudan University, in China, measured blood GFAP levels in 60 Parkinson’s patients without cognitive impairment, 63 with mild cognitive impairment, and 24 with dementia. Blood samples from 15 healthy people without a history of neurological or psychiatric disorders were analyzed as controls.

There were no significant differences between the groups in terms of age, sex ratio, or years of education. As expected, patients with dementia performed significantly worse on the Mini Mental State Examination (MMSE), a standardized measure of cognition, relative to the other groups.

Among all the samples, blood GFAP levels were significantly associated with the participants’ age, but not with sex. There were no significant links between these levels and patients’ disease duration, stage, or levodopa equivalent dose (the total dose of Parkinson’s medications).

After adjusting for age, the results showed that blood GFAP levels were significantly higher in Parkinson’s patients with dementia as compared with the other patients or healthy controls. Patients with mild cognitive impairment also showed significantly higher GFAP levels than controls.

In addition, among Parkinson’s patients, higher GFAP levels in the blood were significantly associated with lower scores on the MMSE, indicating cognitive impairment.

Group analyses revealed that this significant link was true for patients with mild cognitive impairment or dementia, but not for those with normal cognition.

These findings suggest “the presence of reactive astrogliosis in the early phase of cognitive impairment in PD,” the team wrote.

Statistical analyses suggested that GFAP levels could distinguish between Parkinson’s patients with dementia and those with normal cognition with high accuracy. These levels also showed high accuracy in discriminating between patients with dementia and those with MCI or those without dementia — including both MCI and cognitively normal groups.

However, blood GFAP levels could not be used to accurately divide patients with mild cognitive impairment from those without cognitive decline.

[Blood] GFAP measurement may be useful as a marker for predicting the transition from [mild cognitive impairment] to dementia in [Parkinson’s].

To further assess GFAP’s utility to predict cognitive changes in Parkinson’s, 31 of the patients with mild cognitive impairment were followed for an average of about four years. During this time, 10 of these patients — dubbed converters — progressed to dementia.

Patients who progressed to dementia had significantly higher blood GFAP levels at the start of follow-up. An optimal cut-off value of 100.2 picograms/mL was able to separate converters from non-converters with a very high level of accuracy.

This cut-off value showed a 90% sensitivity, or the percentage of converters being correctly identified, as well as an 81% specificity — the percentage of non-converters being accurately ruled out.

Other markers of neuronal damage, such as neurofilament light chain, Tau, and pTau181, did not show significant differences between converters and non-converters, and therefore had a poor discriminating potential.

“We demonstrate that the levels of [blood] GFAP are elevated in PD patients with cognitive impairment, but not in PD patients with normal cognition,” the researchers wrote.

Among the study’s limitations were its small size and the use of relatively broad cognitive measures. Thus, the researchers stressed a need for further studies to validate the results.

“Although the results need to be confirmed with a larger sample size, it is worth noting that [blood] GFAP measurement may be useful as a marker for predicting the transition from MCI to dementia in PD,” the team wrote. “This might be helpful for patient classification in clinical trials or as a follow-up marker.”