1. Medicine
  2. Neuroscience

Plasma extracellular vesicle synaptic proteins as biomarkers of clinical progression in patients with Parkinson’s disease

  1. Chien-Tai Hong
  2. Chen-Chih Chung
  3. Ruan-Ching Yu
  4. Lung Chan  Is a corresponding author
  1. Department of Neurology, Shuang Ho Hospital, Taipei Medical University-Shuang Ho Hospital, Taiwan
  2. Department of Neurology, School of Medicine, College of Medicine Taipei Medical University-Shuang Ho Hospital, Taiwan
  3. Taipei Neuroscience Institute, Taipei Medical University, Taiwan
  4. Division of Psychiatry, University College London, United Kingdom
https://doi.org/10.7554/eLife.87501.3
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  1. Chien-Tai Hong
  2. Chen-Chih Chung
  3. Ruan-Ching Yu
  4. Lung Chan
(2024)
Plasma extracellular vesicle synaptic proteins as biomarkers of clinical progression in patients with Parkinson’s disease
eLife 12:RP87501.
https://doi.org/10.7554/eLife.87501.3
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3 figures, 3 tables and 2 additional files

Figures

Figure 1
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Baseline and follow-up synaptic protein levels in plasma extracellular vesicles (EVs) between patients with Parkinson’s disease (PwP) and healthy controls (HCs).

(A) Representative protein blot images of different synaptic proteins, including SNAP-25, GAP-43, and synaptotagmin-1. Heat shock protein 70 (HSP-70) was the protein loading control. (B–D) Comparison of plasma SNAP-25, GAP-43, and synaptotagmin-1 levels between PwP and HCs at baseline and follow-up. Data are presented using a dot plot displaying the median and first and third quartile values. n.s., nonsignificant.

Figure 1—source data 1

The original blot image of the representative GAP-43 (A), synaptotagmin-1 (B), SNAP-25 (C), and HSP-70 (D).

https://cdn.elifesciences.org/articles/87501/elife-87501-fig1-data1-v1.pdf
Figure 2
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Heatmap of the association between baseline plasma extracellular vesicle (EV) synaptic protein levels and clinical assessment parameters at follow-up in patients with Parkinson’s disease (PwP).

The logistic regression model was used to assess the baseline plasma EV SNAP-25, GAP-43, and synaptotagmin-1 levels. The motor symptoms were assessed based on the Unified Parkinson’s Disease Rating Scale (UPDRS)-II and UPDRS-III scores and tremor, akinetic rigidity (AR), and postural instability and gait disturbance (PIGD) subscores, and cognitive function was assessed using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores. The association is presented using standardized β values. Detailed results of the regression model are provided in Supplementary file 1. *p<0.05; **p<0.01.

Figure 3
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Changes in estimated marginal means of Unified Parkinson’s Disease Rating Scale (UPDRS)-II total scores.

(A) and postural instability and gait disturbance (PIGD) subscores (B) after adjustment for age, sex, and disease duration in patients with Parkinson’s disease (PwP) with (n=36) and without (n=66) elevated levels of any one plasma extracellular vesicle synaptic protein (first quartile) at baseline and follow-up. Data are presented as means with 95% confidence intervals. n.s., nonsignificant.

Tables

Table 1
Demographic data of study participants.
HCs (n = 43)PwP (n = 101)
Age (y)65 (10.24)69 (7.76)
Women1548
Baseline
 MMSE27 (3.92)26 (4.15)
 MoCA23 (4.63)21 (5.70)
 Disease duration (y)-2 (2.24)
 UPDRS-II-8 (5.58)
 UPDRS-III-22 (9.30)
1-year follow-up
 MMSE28 (4.12)27 (5.61)
 MoCA24 (5.82)23 (6.45)
 UPDRS-II-11 (6.41)
 UPDRS-III-19 (9.39)

  1. Data is presented as median (standard deviation).

  2. HC = healthy control; PwP = people with Parkinson’s disease; MMSE = Mini-Mental State Examination; MoCA = Montreal Cognitive Assessment; UPDRS = Unified Parkinson’s Disease Rating Scale.

Table 2
The association between the change in plasma EV synaptic protein abundance (between baseline and follow-up) with the change in clinical severity in motor and cognitive domains (between baseline and follow-up) in people with Parkinson’s disease.

A generalized linear model was employed, and the data is presented as coefficient (p-value).

UPDRS-IIUPDRS-IIITremorARPIGDMMSEMoCA
SNAP-25 * follow-up0.218 (0.049)0.312 (0.076)0.004 (0.432)0.016 (0.066)0.009 (0.440)–0.007 (0.932)0.048 (0.647)
GAP-43 * follow-up0.984 (0.031)1.711 (0.018)0.001 (0.972)0.089 (0.011)0.073 (0.115)–0.099 (0.767)–0.054 (0.901)
Synaptomagtin-1 * follow-up1.543 (0.012)2.205 (0.024)0.007 (0.815)0.107 (0.023)0.109 (0.080)–0.361 (0.421)–0.260 (0.661)

  1. UPDRS = Unified Parkinson's Disease Rating Scale; AR = akinetic rigidity; PIGD = postural instability and gait disturbance; MMSE = Mini-Mental Status Examination; MoCA = Montreal Cognitive Assessment.

Table 3
The clinical severity in people with Parkinson’s disease with and without elevated (first quartile) baseline plasma extracellular vesicle (EV) synaptosome-associated protein 25 (SNAP-25), growth-associated protein 43 (GAP-43), and synaptotagmin-1.

p-Value indicates the inter-group comparisons for the changes.

Plasma EVSNAP-25GAP-43Synaptotagmin-1
L (n = 74)H (n = 28)pL (n = 74)H (n = 28)pL (n = 74)H (n = 28)p
UPDRS-
II		Baseline8.26 ± 5.809.04 ± 4.90<0.0018.53 ± 5.678.32 ± 5.33<0.0018.46 ± 5.708.50 ± 5.24<0.001
Follow-up10.38 ± 6.1113.36 ± 6.7210.65 ± 6.3012.64 ± 6.5310.57 ± 6.2512.86 ± 6.58
UPDRS-IIIBaseline22.31 ± 9.5423.89 ± 8.650.25922.22 ± 9.6624.14 ± 8.250.24421.97 ± 9.3724.79 ± 8.930.145
Follow-up20.01 ± 9.3324.21 ± 8.8719.96 ± 9.2524.36 ± 8.9920.04 ± 9.3924.14 ± 8.70
TremorBaseline0.34 ± 0.460.46 ± 0.380.0370.34 ± 0.340.46 ± 0.370.0340.33 ± 0.340.47 ± 0.380.014
Follow-up0.27 ± 0.260.35 ± 0.320.27 ± 0.260.35 ± 0.320.28 ± 0.290.32 ± 0.22
ARBaseline1.04 ± 0.461.09 ± 0.440.3001.03 ± 0.471.11 ± 0.420.3251.03 ± 0.461.13 ± 0.450.195
Follow-up0.96 ± 0.461.10 ± 0.420.95 ± 0.451.12 ± 0.430.96 ± 0.461.10 ± 0.42
PIGDBaseline0.76 ± 0.610.81 ± 0.440.0230.77 ± 0.600.77 ± 0.450.0460.74 ± 0.560.86 ± 0.580.027
Follow-up0.74 ± 0.591.07 ± 0.750.78 ± 0.610.98 ± 0.740.73 ± 0.561.11 ± 0.80
MMSEBaseline25.32 ± 4.4525.29 ± 3.290.48325.58 ± 4.1624.61 ± 4.110.47025.62 ± 3.9124.50 ± 4.690.342
Follow-up24.78 ± 5.9325.14 ± 4.6425.05 ± 5.7924.43 ± 5.1025.23 ± 5.6123.96 ± 5.50
MoCABaseline20.68 ± 6.0021.21 ± 5.000.83421.14 ± 5.7720.04 ± 5.620.89921.12 ± 5.3320.07 ± 6.690.926
Follow-up20.60 ± 6.8521.46 ± 5.3721.10 ± 6.5520.18 ± 6.3021.19 ± 6.3319.93 ± 6.80

  1. L = second to fourth quartile at baseline; H = first quartile at baseline; UPDRS = Unified Parkinson’s Disease Rating Scale; AR = akinetic rigidity; PIGD = postural instability and gait disturbance; MMSE = Mini-Mental Status Examination; MoCA = Montreal Cognitive Assessment.

Additional files

Supplementary file 1

Association between the baseline plasma EV synaptic proteins with the clinical severity in people with Parkinson’s disease at follow-up with the adjustment of age, sex, disease duration, and the baseline severity of corresponding item, presented as standardized β and p-values.

UPDRS, Unified Parkinson’s Disease Rating Scale; AR, akinetic rigidity; PIGD, postural instability and gait disturbance; MMSE, Mini-Mental Status Examination; MoCA, Montreal Cognitive Assessment.

https://cdn.elifesciences.org/articles/87501/elife-87501-supp1-v1.docx
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https://cdn.elifesciences.org/articles/87501/elife-87501-mdarchecklist1-v1.docx

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  1. Chien-Tai Hong
  2. Chen-Chih Chung
  3. Ruan-Ching Yu
  4. Lung Chan
(2024)
Plasma extracellular vesicle synaptic proteins as biomarkers of clinical progression in patients with Parkinson’s disease
eLife 12:RP87501.
https://doi.org/10.7554/eLife.87501.3