Metabolites and Biomarker Compounds of Neurodegenerative Diseases in Cerebrospinal Fluid
Abstract
:1. Introduction
2. Glucose- and Neurotransmitter-Related CSF Metabolites
2.1. Glucose-Related CSF Metabolites
2.1.1. Glucose
2.1.2. Fructose
2.1.3. Urate
2.1.4. Lactate
2.2. Dopaminergic and Serotonergic Neurotransmitter-Related CSF Metabolites
3. Changes in CSF Compounds Caused by Neurodegeneration
3.1. Alzheimer’s Disease-Related Substances
3.2. Parkinson’s Disease and Other Neurodegenerative-Disease-Related Substances
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
Aβ1-42 | amyloid-β(1-42) |
ABCG2 | ATP-binding cassette transporter G2 |
AD | Alzheimer’s disease |
AE2 | anion exchange protein 2 |
APP | amyloid precursor protein |
AQP1 | aquaporin 1 |
BBB | blood–brain barrier |
BCRP | breast cancer resistance protein |
BCSFB | blood–cerebrospinal fluid barrier |
CBD | corticobasal degeneration |
CBS | corticobasal syndrome |
Ccf-mtDNA | circulating cell-free mitochondrial DNA |
CP | choroid plexus |
CPE | choroid plexus epithelial |
CSF | cerebrospinal fluid |
DLB | dementia with Lewy bodies |
FDG | fluorodeoxyglucose |
FTD | frontotemporal dementia |
GLUT | glucose transporter |
HIAA | hydroxyindoleacetic acid |
iNPH | idiopathic normal pressure hydrocephalus |
IPAD | intravascular periarterial drainage |
ISF | interstitial fluid |
miRNA | microRNA |
MS | multiple sclerosis |
MSA | multiple system atrophy |
NfL | neurofilament light chain |
Nlgn1 | neuroligin-1 |
NMR | nuclear magnetic resonance |
PD | Parkinson’s disease |
PSP | progressive supranuclear palsy |
P-tau | Phosphorylated tau |
SGLT2 | sodium/glucose cotransporter 2 |
S100B | calcium-binding protein B |
T-tau | total tau |
VDBT | vascular dementia of the Binswanger’s type |
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Molecules | Apical Side | Basal Side |
---|---|---|
H2O | AQP1 | AQP1 |
Na+, K+ | Na+−K+−ATPase | |
Na+, K+, 2Cl− | NKCC1 | |
Na+, H+ | NHE1 | |
Na+, HCO3− | NBCe2 | NBCn1 |
Na+, Cl−, HCO3− | Ncbe | |
Cl−, HCO3− | AE2 | |
Cl− | Clir, VRAC | |
K+ | Kir7.1, Kv |
Ions and Osm. | Rabbit 4,7 | Dog 7 | Human 7 | Human 8 |
---|---|---|---|---|
Na+, mEq/L | 149 | 151 | 147 | 137 ± 1.8 |
K+, mEq/L | 2.9 | 2.98 | 2.9 | 2.8 ± 0.1 |
Cl−, mEq/L | 130 | 132.5 | 113 | 122 ± 1.9 |
pH | 7.27 | 7.42 | 7.31 | 7.43 ± 0.02 |
Osm. (mOsm/L) | 305.2 | 305.2 | 289 | n/a |
CSF Compounds | Related Disorders | Expression | Cited Papers | |
---|---|---|---|---|
(a-1) | glucose | aging | inc | [29] |
diabetes mellitus | inc | [30] | ||
bacterial meningitis | dec | [31] | ||
Parkinson’s disease | dec | [33] | ||
(a-2) | fructose | Parkinson’s disease | inc | [43] |
multiple sclerosis | inc | [44] | ||
(a-3) | urate | BBB impairment | inc | [46] |
VDBT | inc | [56] | ||
(a-4) | lactate | aging | inc | [29,59] |
Parkinson’s disease | inc | [60] | ||
multiple sclerosis | inc | [44] | ||
(b-1) | dopaminergic | Parkinson’s disease | dec | [62] |
metabolites | ||||
(b-2) | 5-HIAA | Parkinson’s disease | dec | [63] |
MSA | dec | [63] |
Diseases | Related CSF Compounds | inc/dec | Cited Papers | |
---|---|---|---|---|
(a) | Alzheimer’s | amyloid-b (1-42) | dec | [66,67] |
disease | total tau | inc | [66,67] | |
phosphorylated tau | inc | [66,67] | ||
neurogranin | inc | [68,69] | ||
neuroligin-1 | dec | [71] | ||
microRNAs | inc/dec | [73,74] | ||
Man-transferrin | inc | [75] | ||
ccf-mtDNA | dec | [76] | ||
(b) | Parkinson’s | total α-synuclein | dec | [77,78,79,80] |
disease | p-α-synuclein | inc | [79,81] | |
oligomeric a-synuclein | inc | [62,82] | ||
NfL | n.s./inc | [62,80] | ||
S100B | dec | [80] | ||
neurogranin | dec | [83] | ||
microRNAs | inc/dec | [84] | ||
ccf-mtDNA | dec | [85] | ||
(c) | Parkinsonism | α-synuclein | dec | [77,78,79,80] |
NfL | inc | [80,86] | ||
neurogranin | dec | [83] | ||
(DLB) | S100B | inc | [80] | |
(MSA) | chromogranin A | dec | [87] | |
(PSP) | NfL/p-tau ratio | inc | [88] | |
microRNAs | inc/dec | [89] | ||
(iNPH) | Ab oligomers (10-20) | inc | [72] |
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Wakamatsu, K.; Chiba, Y.; Murakami, R.; Miyai, Y.; Matsumoto, K.; Kamada, M.; Nonaka, W.; Uemura, N.; Yanase, K.; Ueno, M. Metabolites and Biomarker Compounds of Neurodegenerative Diseases in Cerebrospinal Fluid. Metabolites 2022, 12, 343. https://doi.org/10.3390/metabo12040343
Wakamatsu K, Chiba Y, Murakami R, Miyai Y, Matsumoto K, Kamada M, Nonaka W, Uemura N, Yanase K, Ueno M. Metabolites and Biomarker Compounds of Neurodegenerative Diseases in Cerebrospinal Fluid. Metabolites. 2022; 12(4):343. https://doi.org/10.3390/metabo12040343
Chicago/Turabian StyleWakamatsu, Keiji, Yoichi Chiba, Ryuta Murakami, Yumi Miyai, Koichi Matsumoto, Masaki Kamada, Wakako Nonaka, Naoya Uemura, Ken Yanase, and Masaki Ueno. 2022. "Metabolites and Biomarker Compounds of Neurodegenerative Diseases in Cerebrospinal Fluid" Metabolites 12, no. 4: 343. https://doi.org/10.3390/metabo12040343
APA StyleWakamatsu, K., Chiba, Y., Murakami, R., Miyai, Y., Matsumoto, K., Kamada, M., Nonaka, W., Uemura, N., Yanase, K., & Ueno, M. (2022). Metabolites and Biomarker Compounds of Neurodegenerative Diseases in Cerebrospinal Fluid. Metabolites, 12(4), 343. https://doi.org/10.3390/metabo12040343