Biomarkers of neurodegeneration and glial activation validated in Alzheimer's disease assessed in longitudinal cerebrospinal fluid samples of Parkinson's disease

被引：32

作者：

Bartl, Michael ^{[1
]}

Dakna, Mohammed ^{[1
]}

Galasko, Douglas ^{[2
]}

Hutten, Samantha J. ^{[3
]}

Foroud, Tatiana ^{[4
]}

Quan, Marian ^{[5
]}

Marek, Kenneth ^{[6
]}

Siderowf, Andrew ^{[7
]}

Franz, Jonas ^{[8
,9
,10
]}

Trenkwalder, Claudia ^{[11
,12
]}

Mollenhauer, Brit ^{[1
,11
]}

机构：

[1] Univ Med Ctr Goettingen, Dept Neurol, Gottingen, Germany

[2] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA

[3] Michael J Fox Fdn Parkinsons Res, New York, NY USA

[4] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN USA

[5] Roche Diagnost, Indianapolis, IN USA

[6] Inst Neurodegenerat Disorders, New Haven, CT USA

[7] Univ Penn, Perelman Sch Med, Dept Neurol, Philadelphia, PA USA

[8] Univ Med Ctr Gottingen, Inst Neuropathol, Gottingen, Germany

[9] Univ Gottingen, Campus Inst Dynam Biol Networks, Gottingen, Germany

[10] Max Planck Inst Expt Med, Gottingen, Germany

[11] Paracelsus Elena Klin, Kassel, Germany

[12] Univ Med Ctr Goettingen, Dept Neurosurg, Gottingen, Germany

来源：

PLOS ONE | 2021年 / 16卷 / 10期

关键词：

ALPHA-SYNUCLEIN; DEMENTIA;

D O I：

10.1371/journal.pone.0257372

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Aim Several pathophysiological processes are involved in Parkinson's disease (PD) and could inform in vivo biomarkers. We assessed an established biomarker panel, validated in Alzheimer's Disease, in a PD cohort. Methods Longitudinal cerebrospinal fluid (CSF) samples from PPMI (252 PD, 115 healthy controls, HC) were analyzed at six timepoints (baseline, 6, 12, 24, 36, and 48 months follow-up) using Elecsys (R) electrochemiluminescence immunoassays to quantify neurofilament light chain (NfL), soluble TREM2 receptor (sTREM2), chitinase-3-like protein 1 (YKL40), glial fibrillary acidic protein (GFAP), interleukin-6 (IL-6), S100, and total alpha-synuclein (alpha Syn). Results alpha Syn was significantly lower in PD (mean 103 pg/ml vs. HC: 127 pg/ml, p<0.01; area under the curve [AUC]: 0.64), while all other biomarkers were not significantly different (AUC NfL: 0.49, sTREM2: 0.54, YKL40: 0.57, GFAP: 0.55, IL-6: 0.53, S100: 0.54, p>0.05) and none showed a significant difference longitudinally. We found significantly higher levels of all these markers between PD patients who developed cognitive decline during follow-up, except for alpha Syn and IL-6. Conclusion Except for alpha Syn, the additional biomarkers did not differentiate PD and HC, and none showed longitudinal differences, but most markers predict cognitive decline in PD during follow-up.

引用

页数：15

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