MDS Presentation on PPMI- Association between CSF biomarkers and clinical phenotype of early Parkinson’s disease

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Poster Number: 111
Location: Linear Park Marquee #2
Poster Session Date: Sunday, 6/17/2012
Poster Session Time: 8:00-19:00
Poster Presentation Time: 12:30 – 14:00

Title: Association between CSF biomarkers and clinical phenotype of early Parkinson?s disease in the Parkinson?s Progression Marker Initiative (PPMI)

Authors: Ju-Hee Kang, Chelsea Caspell, Chris Coffey, Peggy Taylor, Mark Frasier, Kenneth Marek, John Q. Trojanowski, Leslie M. Shaw, and the Parkinson?s Progression Marker Initiative

Background: There is substantial heterogeneity in the onset and progression of clinical phenotypes of Parkinson?s disease (PD) such as cognitive impairment, a common non-motor complication that progresses to overt dementia in ~80% of PD patients with long standing disease. The PPMI is an ongoing international multicenter study to assess progression of clinical features, imaging and biochemical biomarkers in de novo PD compared to healthy controls (HC) and in PD subtypes. The purpose of this study was to explore the association of CSF biomarkers (Ab1-42, t-tau, p-tau181 and a-synuclein) with clinical features in de novo drug-naive PD patients enrolled in the PPMI study.

Methods: Baseline CSF samples were obtained from 106 PPMI individuals (39 HC and 67 PD). CSF Ab1-42, t-tau and p-tau181 were measured using the multiplex xMAP-Luminex platform with Alz-Bio3 immnoassay kits, and CSF a-synuclein (a -syn) was measured by ELISA. Demographics, H&Y stage, UPDRS, smell test (UPSIT) score, neuropsychological and cognitive assessments, CSF hemoglobin (Hgb) level and dopamine transporter (DaT) scan were evaluated

Results: Mean age (HC, 59±13 vs. PD, 62±10), gender distribution (HC, M:F=22:17 vs. PD, M:F=41:26) and CSF Hgb level were not significantly different. Mean score of UPDRS motor function test in PD was significantly higher than in HC, and scores of cognitive assessments (MoCA, SDMT, semantic fluency, HVLT-R initial and delayed recall and WMS-III LNS) were significantly lower in PD than in HC. We found that CSF t-tau, p-tau181 and t-tau/Ab1-42 ratio in PD were significantly lower than HC. PD patients showed significantly lower level of CSF a-syn compared with HC, which was not changed by adjustment of CSF Hgb (Table). CSF Ab1-42 level in PD was lower than HC with marginal significance. CSF a-syn was significantly correlated with t-tau (r=0.7787, p<0.0001) or p-tau181 (r=0.4721, p<0.0001), but not with Ab1-42 (r=0.1341, p=0.1704).

Conclusions: We found that the level of tau proteins (t-tau and p-tau181) and a-syn in CSF of these untreated PD patients were significantly lower than those of HC, and that CSF a-syn concentration was significantly correlated with the concentrations of CSF tau proteins. Further investigations are planned to test the predictive performance of the biomarkers for disease progression.

Table. Comparison of CSF biomarker levels between healthy control (HC) and PD patients.

CSF biomarkers

HC (N=39)

PD (N=67)

p value$

Ab1-42 (pg/mL)

242.8 ± 49.95

231.5 ± 45.91

0.0968

t-tau (pg/mL)

53.9 ± 19.33

46.6 ± 24.65

0.0361

p-tau181 (pg/mL)

24.9 ± 8.45

21.2 ± 7.82

0.0109

a-syn (pg/mL)

1264 ± 425.7

1101 ± 618.6

0.0194

a-syn (pg/mL)*

1267 ± 443.5

1041 ± 487.2

0.0242

a-syn (pg/mL)#

1269 ± 435.2

1037 ± 499.7

0.0104

t-tau/Ab1-42

0.240 ± 0.141

0.214 ± 0.153

0.0494

p-tau181/Ab1-42

0.113 ± 0.075

0.099 ± 0.061

0.1319

p-tau181/t-tau

0.491 ± 0.160

0.540 ± 0.260

0.7064

a-syn/Ab1-42

5.6 ± 3.05

4.9 ± 2.98

0.1159

a-syn/t-tau

24.4 ± 7.23

25.0 ± 8.61

0.9373

a-syn/p-tau181

53.7 ± 18.94

52.4 ± 21.94

0.5511

Hgb (ng/mL)

121.7 ± 324.6

599.3 ± 1837

0.1156

$Mann-Whitney U test.

*Mean ± S.D. of a-syn levels after exclusion of samples with CSF Hgb > 200 ng/mL. The ranges of a-syn in HC (N=33) and PD (N=48) were 491.9 ? 2025 and 227.4 ? 2290 pg/mL, respectively.

#Mean ± S.D. of a-syn levels after exclusion of samples with CSF Hgb > 500 ng/mL. The range of a-syn in HC (N=37) and PD (N=55) were 491.9 ? 2025 and 227.4 ? 2295, respectively.

The mean±S.D. value was from 66 PD samples due to removal of 1 sample with CSF Hgb level above upper limit of quantitation.