Exploration of Neuroprotective Therapy

Table 1. Selected ALS biomarker candidates, with possible usage.

Biomarker methodology	Intended analyses	Commonly measured tissues	Biomarkers of particular interest	Reference(s)
Imaging biomarkers
MRI-DTI: FA, MD as proxies of white-matter fiber/axonal integrity	diagnosis, progression	CST, esp. brainstem	+	[27, 44]
[¹⁸F]FEDV-PET: high spatial-resolution index of excessive oxidative stress	diagnosis, prediction?	CSF diffuses through the BBB	+	[28]
[¹⁸F]FDG-PET: index of reduced oxidative respiration (low ATP)	diagnosis? prognosis?	CSF diffuses through the BBB		[45]
Physiologic biomarkers
MScanFIT MUNE	progression	various muscles		[25, 45]
MUNIX	progression, prediction?	various muscles		[45, 46]
EIM	progression	various muscles		[45]
Chemical biomarkers Protein immunoassay (suggested method)
(Simoa^®): NF-L	prediction, diagnosis, prognosis?	CSF	+	[32, 33]
(Simoa^®): NF-L	prediction, diagnosis, prognosis?	blood	+	[32, 33]
(MSD): pNF-H	requires further study	CSF		[32]
(MSD): pNF-H	requires further study	plasma		[33]
(ELISA): PGRN	requires further study	CSF		[33, 47]
(ELISA): PGRN	requires further study	blood		[33, 47, 48]
(nLC-MS): TDP-43	diagnosis, progression	CSF	+	[33, 49]
		PBMC		[33]
		plasma		[33]
nLC-MS: multiprotein expression profiles	diagnosis, progression	PBMC	+	[33]
Cell-based assays: stress granules & associated proteins	requires further study	Cell-based assays		[33]
Immunoassay: cytokines, pro-inflammatory	requires further study	CSF		[32]
Immunoassay: cytokines, pro-inflammatory	requires further study	blood		[32, 33]
Hematology exam (photometry): CK	diagnosis, progression	blood	+	[33, 50, 51]
EV NGS: extracellular RNA	diagnosis?	CSF		[33]
EV NGS: extracellular RNA	diagnosis?	blood		[33]
Structural inspection, cellular-respiratory assays: damaged mitochondria	diagnosis?	all tissues	+	[33]

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[¹⁸F]FDG-PET: [¹⁸F]fluorodeoxyglucose-positron emission tomography; [¹⁸F]FEDV-PET: [¹⁸F]fluoroedaravone-positron emission tomography; BBB: blood-brain barrier; CK: creatine kinase; CSF: cerebrospinal fluid; CST: corticospinal tract; EIM: electrical impedance myography; EV: extracellular vesicle; FA: fractional anisotropy; MD: mean diffusivity; MRI-DTI: magnetic resonance imaging-based diffusion tensor imaging; MSD: Meso Scale Discovery; MUNE: motor unit number estimation; MUNIX: motor unit number index; NF-L: neurofilament light chain; NGS: next-generation sequencing; nLC-MS: nano liquid chromatography-mass spectrometry; PBMC: peripheral blood mononuclear cells; PGRN: progranulin; pNF-H: phosphorylated neurofilament heavy chain; Simoa^®: single-molecule array immunoassay; TDP-43: transactive response DNA binding protein 43.

Declarations

Author contributions

CAS: Conceptualization, Writing—original draft, Writing—review & editing, Project administration, Investigation. CB: Writing—review & editing, Investigation. LM: Writing—review & editing, Investigation, Visualization. All authors read and approved the submitted version.

Conflicts of interest

The first author, Christopher A. Shaw, holds founder shares in Neurodyn Corp and its subsidiary, Alpha Cognition, biotechnology companies that are developing treatments for neurological disorders but are not involved in biomarker studies. Christopher A. Shaw, who is the Associate Editor of Exploration of Neuroprotective Therapy, had no involvement in the decision-making or the review process of this manuscript. The other authors declare no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

Not applicable.

Copyright

Publisher’s note

Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.

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