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Cerebrospinal fluid alpha-synuclein, amyloid beta, total tau, and phosphorylated tau in tremor-dominant Parkinson’s disease

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Abstract

Background

Protein misfolding within specific brain regions is a common characteristic of neurodegenerative diseases, such as Alzheimer's disease and Parkinson’s disease (PD). Therefore, a common term often used for these disorders is “proteinopathy”. Currently, there has been increasing attention toward the overlap of pathogenesis between proteinopathies.

Aims

We aimed to explore the cross-sectional and longitudinal level of the CSF α-synuclein (α-syn), amyloid βeta (Aβ1-42), total tau (t-tau), and phosphorylated tau (p-tau) in PD subjects with tremor dominant (TD) and a non-tremor dominant (nonTD) subtype from the Parkinson Progression Markers Initiative (PPMI).

Methods

We enrolled 411 early-stage PD patients and 187 healthy controls (HCs) from the PPMI. We compared the level of CSF biomarkers at four time points including baseline, 6 months, 1 year, and 2 years. To investigate longitudinal changes in CSF proteins within each group, we used linear mixed models.

Results

The level of CSF biomarkers was significantly lower in PD patients compared to HCs at any visit. Moreover, there was no statistically significant difference in the level of CSF α-syn, Aβ1-42, t-tau, and p-tau between PD-TD and PD-nonTD. Longitudinal analysis showed significant CSF α-syn reduction after one year from baseline in PD-TD patients (P = 0.047). Also, there was a significant reduction in the level of CSF Aβ1-42 after two years in PD-nonTD patients but not HCs and PD-TD (P = 0.033).

Conclusion

Our results indicate that different patterns in longitudinal changes of CSF biomarkers could be due to different pathophysiological mechanisms involved in each PD motor subtype.

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Data availability

The datasets analyzed during the current study are available upon request with no restriction.

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Acknowledgements

PPMI–a public-private partnership–is funded by the Michael J. Fox Foundation for Parkinson’s Research funding partners 4D Pharma, Abbvie, Acurex Therapeutics, Allergan, Amathus Therapeutics, ASAP, Avid Radiopharmaceuticals, Bial Biotech, Biogen, BioLegend, Bristol-Myers Squibb, Calico, Celgene, Dacapo Brain Science, Denali, The Edmond J. Safra Foundation, GE Healthcare, Genentech, GlaxoSmithKline, Golub Capital, Handl Therapeutics, Insitro, Janssen Neuroscience, Lilly, Lundbeck, Merck, Meso Scale Discovery, Neurocrine Biosciences, Pfizer, Piramal, Prevail, Roche, Sanofi Genzyme, Servier, Takeda, Teva, UCB, Verily, and Voyager Therapeutics.

Funding

We do not have any financial support for this study.

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FN and FS: designed the study, analyzed the data, and wrote the paper; FN, FS and AK: collected data, analyzed and interpreted the data, and wrote the draft version of the manuscript. The manuscript was revised and approved by all authors.

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Correspondence to Fardin Nabizadeh.

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Since the data in this paper were obtained from the PPMI database (ppmi.loni.usc.edu), it does not include any research involving human or animal subjects.

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Nabizadeh, F., Sodeifian, F. & Kargar, A. Cerebrospinal fluid alpha-synuclein, amyloid beta, total tau, and phosphorylated tau in tremor-dominant Parkinson’s disease. Acta Neurol Belg 123, 1429–1437 (2023). https://doi.org/10.1007/s13760-023-02251-9

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