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
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
收藏
页数:15
相关论文
共 23 条
[21]   Understanding disease progression and improving Alzheimer's disease clinical trials: Recent highlights from the Alzheimer's Disease Neuroimaging Initiative [J].
Veitch, Dallas P. ;
Weiner, Michael W. ;
Aisen, Paul S. ;
Beckett, Laurel A. ;
Cairns, Nigel J. ;
Green, Robert C. ;
Harvey, Danielle ;
Jack, Clifford R., Jr. ;
Jagust, William ;
Morris, John C. ;
Petersen, Ronald C. ;
Saykin, Andrew J. ;
Shaw, Leslie M. ;
Toga, Arthur W. ;
Trojanowski, John Q. ;
Aisen, Paul ;
Weiner, Michael ;
Petersen, Ronald ;
Trojanowki, John Q. ;
Toga, Arthur W. ;
Beckett, Laurel ;
Morris, John ;
Khachaturian, Zaven ;
Sorensen, Greg ;
Carrillo, Maria ;
Kuller, Lew ;
Raichle, Marc ;
Paul, Steven ;
Davies, Peter ;
Fillit, Howard ;
Hefti, Franz ;
Holtzman, David ;
Mesulam, M. Marcel ;
Potter, William ;
Snyder, Peter ;
Montine, Tom ;
Jimenez, Gustavo ;
Donohue, Michael ;
Gessert, Devon ;
Harless, Kelly ;
Salazar, Jennifer ;
Cabrera, Yuliana ;
Walter, Sarah ;
Hergesheimer, Lindsey ;
Harvey, Danielle ;
Bernstein, Matthew ;
Fox, Nick ;
Thompson, Paul ;
Schuff, Norbert ;
DeCArli, Charles .
ALZHEIMERS & DEMENTIA, 2019, 15 (01) :106-152
[22]   The Inflammatory Marker YKL-40 Is Elevated in Cerebrospinal Fluid from Patients with Alzheimer's but Not Parkinson's Disease or Dementia with Lewy Bodies [J].
Wennstrom, Malin ;
Surova, Yulia ;
Hall, Sara ;
Nilsson, Christer ;
Minthon, Lennart ;
Hansson, Oskar ;
Nielsen, Henrietta M. .
PLOS ONE, 2015, 10 (08)
[23]   Soluble TREM2 is elevated in Parkinson's disease subgroups with increased CSF tau [J].
Wilson, Edward N. ;
Swarovski, Michelle S. ;
Linortner, Patricia ;
Shahid, Marian ;
Zuckerman, Abigail J. ;
Wang, Qian ;
Channappa, Divya ;
Minhas, Paras S. ;
Mhatre, Siddhita D. ;
Plowey, Edward D. ;
Quinn, Joseph F. ;
Zabetian, Cyrus P. ;
Tian, Lu ;
Longo, Frank M. ;
Cholerton, Brenna ;
Montine, Thomas J. ;
Poston, Kathleen L. ;
Andreasson, Katrin I. .
BRAIN, 2020, 143 :932-943