Neurofilament light chain as a mediator between LRRK2 mutation and dementia in Parkinson’s disease
npj Parkinson's Disease, ISSN: 2373-8057, Vol: 9, Issue: 1, Page: 132
2023
- 7Citations
- 13Captures
- 2Mentions
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Metrics Details
- Citations7
- Citation Indexes7
- Captures13
- Readers13
- 13
- Mentions2
- News Mentions2
- News2
Most Recent News
NfL levels may mediate link between dementia, LRRK2 variants
Scientists have discovered that long-term changes in a biomarker of nerve damage, called neurofilament light chain (NfL), could be used to predict cognitive decline in
Article Description
Elevated neurofilament light chain (NfL) levels have been associated with dementia in idiopathic Parkinson’s disease (iPD). To examine the baseline and longitudinal changes in NfL levels in GBA-PD, SNCA-PD, and LRRK2-PD and further investigate the association between these genetic mutations, NfL, and dementia in PD. We analyzed data from the Parkinson’s Progression Markers Initiative (PPMI), including 184 healthy controls (HC) and 617 PD categorized as iPD (n = 381), LRRK2-PD (n = 142), GBA-PD (n = 76) and SNCA-PD (n = 18). Analysis of covariance (ANCOVA) or linear mixed-effect models were used to compare the baseline or dynamic NfL levels between groups. We then explored the relationship between genetic mutations, serum NfL levels, and conversion to dementia using mediation analysis. After adjusting for confounding factors, SNCA-PD exhibited higher baseline serum NfL levels than iPD. Regarding longitudinal changes, SNCA-PD showed the highest increase rate in estimated NfL levels (2.43 pg/mL per year), while LRRK2-PD experienced the slowest increase rate (0.52 pg/mL per year). Mediation analysis indicated that higher estimated NfL level changes were associated with faster cognitive decline (β = 0.591, p = 0.026). Specifically, the relationship between LRRK2 and dementia was mediated by the estimated NfL level change (β = −0.717, p < 0.05). Longitudinal changes in serum NfL levels may serve as a biomarker for cognitive decline in Parkinson’s disease. Moreover, compared to iPD, the slower progression of dementia in LRRK2-PD may be partially attributed to a slower increase in NfL levels.
Bibliographic Details
Springer Science and Business Media LLC
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