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Plasma Biomarkers and Disease Prognosis in Mild Cognitive Impairment with Lewy Bodies
Paul C Donaghy1, Jahfer Hasoon1, Calum A Hamilton1
1Translational and Clinical Research Institute and NIHR Newcastle Biomedical Research Centre, Newcastle University, Newcastle upon Tyne, UK.
Background:
Little is known about the prognostic value of plasma biomarkers in mild cognitive impairment with Lewy bodies (MCI-LB).
Objectives:
To investigate the association of four plasma biomarkers with disease progression in MCI.
Methods:
Plasma amyloid-beta (Aβ)42/40, glial fibrillary acidic protein (GFAP), neurofilament light (NfL), and phosphorylated tau 181 (pTau181) were measured at baseline in a longitudinal MCI cohort (n = 131).
Results:
Baseline plasma NfL was associated with increased risk of dementia/death in the entire cohort. In MCI-LB, baseline plasma NfL, GFAP, and pTau181 were associated with increased risk of dementia/death and increased cognitive decline measured by the Addenbrooke's Cognitive Examination-Revised.
Conclusions:
pTau181, GFAP, and NfL are associated with more rapid disease progression in MCI-LB and, with further validation, could be useful to support prognosis and stratification for clinical practice and treatment trials. Further work, including clinicopathological studies, is needed to understand the biological correlates of these markers in MCI-LB. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Insights
Plasma biomarkers like neurofilament light (NfL), GFAP, and pTau181 show promise for predicting disease progression in mild cognitive impairment with Lewy bodies (MCI-LB). These markers may aid in prognosis and clinical trial stratification.
Area of Science:
- Neurology
- Biomarker Research
- Neurodegenerative Diseases
Background:
- Prognostic value of plasma biomarkers in mild cognitive impairment with Lewy bodies (MCI-LB) is largely unknown.
- MCI-LB represents a critical stage for early intervention and understanding disease trajectory.
Purpose of the Study:
- To investigate the association between specific plasma biomarkers and disease progression in individuals with MCI.
- To determine the prognostic utility of plasma amyloid-beta (Aβ)42/40, glial fibrillary acidic protein (GFAP), neurofilament light (NfL), and phosphorylated tau 181 (pTau181) in MCI.
Main Methods:
- A longitudinal cohort of 131 individuals with MCI was studied.
- Plasma levels of Aβ42/40, GFAP, NfL, and pTau181 were measured at baseline.
- Disease progression was assessed by risk of dementia/death and cognitive decline using the Addenbrooke's Cognitive Examination-Revised.
Main Results:
- Plasma NfL at baseline predicted increased risk of dementia or death in the overall MCI cohort.
- In MCI-LB, baseline plasma NfL, GFAP, and pTau181 were significantly associated with an increased risk of dementia/death.
- These biomarkers also correlated with accelerated cognitive decline in the MCI-LB subgroup.
Conclusions:
- Plasma pTau181, GFAP, and NfL are linked to faster disease progression in MCI-LB.
- These biomarkers show potential for supporting prognosis and patient stratification in clinical practice and treatment trials for MCI-LB.
- Further research, including clinicopathological studies, is necessary to elucidate the biological underpinnings of these markers in MCI-LB.
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