Brain-Specific Cytoskeletal Damage Markers in Cerebrospinal Fluid: Is There a Common Pattern between Amyotrophic Lateral Sclerosis and Primary Progressive Multiple Sclerosis?
Abstract
:1. Introduction
2. Pathophysiology of ALS
3. Pathophysiology of Progressive Multiple Sclerosis (MS)
4. Physiology of Cerebrospinal Fluid (CSF) and Its Relationship with Brain Specific Proteins in CSF
5. CSF Markers of Neuroaxonal Damage
5.1. Neurofilaments
5.1.1. Neurofilaments (NF) in ALS
Marker | Method | Sample Size | Finding | Correlation with Progression Rate | Reference |
---|---|---|---|---|---|
NfL | ELISA | 12 ALS, 11 AD, 34 control | ALS > AD | not reported | [68] |
ELISA | 60 sALS, 19 fALS, 206 OND | ALS > reference > control | yes | [71] | |
ELISA | 32 ALS, 26 ALS-mimic | ALS > ALS-mimic | not reported | [70] | |
ELISA | 37 ALS, 25 CIDP, 21 OND | ALS > CIDP and OND | yes | [72] | |
ECL | 38 ALS, 20 control | ALS > control | not reported | [74] | |
NfH | ELISA | ALS 69, 33 Control | ALS > control | yes | [69] |
ELISA | 32 ALS, 26 ALS-mimic | ALS > ALS-mimic | not reported | [70] | |
ECL | 50 ALS, 73 controls | ALS > control | not reported | [75] | |
ELISA | 20 ALS | Higher level is associated with rapid progression | yes | [73] |
5.1.2. Neurofilaments (NF) in Primary Progressive Multiple Sclerosis (PPMS)
Marker | Method | Sample Size | Finding | Correlation with Disability | Reference |
---|---|---|---|---|---|
NfL | Dot Blot | 16 PPMS, 13 SPMS, 6 PPMS, 36 IND and NIND | PMS > RRMS > control | yes | [57] |
ELISA | 21 RRMS, 20 SPMS, 10 PPMS | Non-measurable | no | [78] | |
ELISA | 65 RRMS, 10 SPMS, 20 PPMS | Sig. correlation between NfL and MSSS at follow up | not reported | [79] | |
ELISA | 33 RRMS, 7 SPMS, 1 PPMS | PMS > RRMS > OND | yes | [80] | |
ELISA | 40 SPMS, 21 PPMS, 26 RRMS, 20 NIND | RRMS > PMS > NIND | not reported | [77] | |
ELISA | 38 RRMS, 25 SPMS, 23 PPMS, 62 CIS, 72 healthy control | RRMS/SPMS/PPMS > control | no | [59] | |
NfH | In-House ELISA technique | 23 SP/PP MS, 11 RRMS, 318 NIND | NfHSMI35 PMS > RRMS | yes | [76] |
ELISA | 21 RRMS, 20 SPMS, 10 PPMS | RRMS = SPMS = PPMS > controls | no | [78] |
5.2. Tau-Protein (Tau)
5.2.1. Tau-Protein (Tau) in Amyotrophic Lateral Sclerosis (ALS)
Marker | Sample | Finding | Relation to Clinical Severity | Reference |
---|---|---|---|---|
t-Tau | 20 sALS, 20 controls | 70% of ALS have high CSF-tau compared to controls | no | [86] |
18 sALS, 75 control | ALS = control | no | [83] | |
67 sALS, 2 fALS, 33 control | ALS > control | no | [69] | |
57 sALS, 110 controls | ALS = controls | no | [84] | |
51 ALS, 23 4R-tau, 23 control | ALS = 4R-Tau = control | yes | [85] |
5.2.2. Tau-Protein (Tau) in Primary Progressive Multiple Sclerosis (PPMS)
Marker | Number | Finding | Correlation to Disability | Reference |
---|---|---|---|---|
t-Tau | 15 RRMS, 11 SPMS, 10 PPMS, 17 ALS, 29 healthy controls | MS > control and ALS 72% of PMS having highly elevated tau compared to 27% of RRMS | not reported | [87] |
84 RRMS, 21 SPMS, 9 PPMS, 60 NIND, 79 IND | RRMS > IND > PMS > NIND | not reported | [90] | |
43 defined MS, 20 CIS, 56 controls (OND) | MS = control | No | [92] | |
50 CIS, 35 RRMS, 8 SPMS, 9 PPMS, 46 control | MS > control | No | [88] | |
32 RRMS, 2 SPMS, 4 PPMS, 19 healthy controls | MS = Control | No | [91] | |
30 RRMS, 9 SPMS, 6 PPMS, 38 healthy controls | MS > control | No | [89] |
5.3. Phosphorylated Tau-Protein (p-Tau)
5.3.1. p-Tau in ALS
5.3.2. p-Tau in PPMS
5.4. Tubulin and Actin
6. Discussion
CSF-Markers of Axonal Damage | PPMS | Reference | ALS | Reference |
---|---|---|---|---|
Neurofilaments | PPMS > healthy controls | [75,76,77,78,79] | ALS > healthy controls | [68,69,70,71,72,73,74] |
t-Tau | PPMS > or = healthy controls | [87,88,89,90,91] | ALS > or = healthy controls | [83,84,85,86] |
p-Tau | PPMS < healthy controls | [93] | ALS < 4-repeat tauopathy | [85] |
7. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
Abbreviations
References
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Abdelhak, A.; Junker, A.; Brettschneider, J.; Kassubek, J.; Ludolph, A.C.; Otto, M.; Tumani, H. Brain-Specific Cytoskeletal Damage Markers in Cerebrospinal Fluid: Is There a Common Pattern between Amyotrophic Lateral Sclerosis and Primary Progressive Multiple Sclerosis? Int. J. Mol. Sci. 2015, 16, 17565-17588. https://doi.org/10.3390/ijms160817565
Abdelhak A, Junker A, Brettschneider J, Kassubek J, Ludolph AC, Otto M, Tumani H. Brain-Specific Cytoskeletal Damage Markers in Cerebrospinal Fluid: Is There a Common Pattern between Amyotrophic Lateral Sclerosis and Primary Progressive Multiple Sclerosis? International Journal of Molecular Sciences. 2015; 16(8):17565-17588. https://doi.org/10.3390/ijms160817565
Chicago/Turabian StyleAbdelhak, Ahmed, Andreas Junker, Johannes Brettschneider, Jan Kassubek, Albert C. Ludolph, Markus Otto, and Hayrettin Tumani. 2015. "Brain-Specific Cytoskeletal Damage Markers in Cerebrospinal Fluid: Is There a Common Pattern between Amyotrophic Lateral Sclerosis and Primary Progressive Multiple Sclerosis?" International Journal of Molecular Sciences 16, no. 8: 17565-17588. https://doi.org/10.3390/ijms160817565