Table 1 Summary of fluid biomarkers and their changes in AD
From: Advances in the development of new biomarkers for Alzheimer’s disease
Biomarker | Study group | Sample | Remark | References |
|---|---|---|---|---|
Aβ1-42/Aβ1-40 | AD n = 57 MCI n = 214 SCD n = 174 NC n = 274 | Plasma CSF | AD Aβ42 and Aβ40 AD ↓ vs NC | [59] |
APP669–711/ Aβ1-42 Aβ1-40/Aβ1-42 | Cohort NCGG AD n = 29 MCI n = 30 NC n = 62 Cohort AIBL AD n = 29 MCI n = 67 NC n = 156 | Plasma CSF | AD plasma composite biomarker and other Aβ bimarkers (including Aβ42) showed significant correlations with Aβ-PET | [60] |
P-Tau | AD n = 26 | CSF | AD CSF P-Tau showed a positive correlation with counts of neurofibrillary tangles (NFT) and neuritic plaques (NP) | [75] |
T-Tau | AD n = 54, MCI n = 75 NC n = 25 | Plasma CSF | T-Tau ↑ in AD | [130] |
Aβ1-40 Aβ1-42 T-Tau | AD/MCI n = 25 NC n = 20 | Plasma | Aβ42↑ in AD Aβ42/Aβ40↑ in AD T-Tau↑ in AD | [131] |
T-Tau P-Tau | AD n = 28, NC n = 23 | CSF | T-tau↑ in AD | [132] |
Aβ1-42 T-Tau | Cohort ADNI: AD n = 179 MCI n = 195 NC n = 189 Cohort BioFINDER: AD n = 61 MCI n = 212 SCD n = 174 NC n = 274 | Plasma CSF | AD Plasma Tau ↑ vs NC and MCI (ADNI cohort) CSF Aβ42 negatively correlated with Plasma Tau (ADNI cohort) AD plasma Tau > Aβ− NC, Aβ+ NC, Aβ− MCI, Aβ+ MCI (ADNI cohort) Aβ+ MCI plasma Tau > Aβ− MCI (ADNI cohort) CSF Aβ42 positively correlated with CSF T-Tau and P-Tau (BioFINDER) | [80] |
NFL, T-Tau | AD n = 156 MCI n = 185 NC n = 279 | Plasma | Plasma NFL AD↑ vs MCI and NC | [97] |
P-Tau, T-Tau | AD n = 40 MCI n = 57 NC n = 172 | Plasma | T-Tau↑ in AD and MCI P-Tau ↑ in AD | [78] |
Neurogranin | AD n = 65 MCI n = 61 NC n = 37 | CSF | Neurogranin ↑ in AD and MCI baseline Neurogranin ↑ in AD and MCI follow-up | [83] |
Neurogranin YKL-40 | AD n = 74 DLB/PDD n = 47 VaD n = 34 FTD n = 33 NC n = 53 | CSF | Neurogranin ↑ in AD and MCI vs NC YKL-40 ↑ in AD vs NC | [84] |
Neurogranin NFL YKL-40 T-tau | AD n = 180 MCI n = 450 NC n = 140 | CSF | Neurogranin ↑ in Aβ+ vs Aβ− NFL ↑ in AD and MCI vs NC YKL-40 ↑ in AD and MCI vs NC T-tau ↑ in AD and MCI vs NC | [87] |
Neurogranin | AD n = 100 MCI n = 40 NC n = 80 | CSF | Neurogranin ↑ in AD and MCI | [85] |
Neurogranin | AD n = 95 MCI n = 173 NC n = 110 | CSF | Neurogranin ↑ in AD and MCI | [86] |
Neurogranin | AD n = 100 genetic AD n = 2 bvFTD n = 20 svFTD n = 21 DLB n = 13 PD n = 31 PSP n = 46 MSA n = 29 NC n = 50 | CSF | Neurogranin ↑ in AD and genetic AD | [90] |
Neurogranin | AD n = 397 MCI n = 114 NC n = 75 | CSF | Neurogranin ↑ in AD | [91] |
Neurogranin | Cross-sectional study AD n = 12, FTD n = 16, NC n = 28 Longitudinal study AD n = 9 FTD n = 10 NC n = 19 | Plasma | Exosomal neurogranin ↓ in AD | [89] |
NFL | Mut AD n = 243 NC n = 162 | CSF Serum | NFL ↑ in AD in serum and CSF | [94] |
IL-1β | AD n = 58 MCI n = 74 NC n = 31 | Serum | IL-1β ↑ in AD and MCI | [101] |
CCL2 (MCP-1) | AD n = 41 NC n = 31 | serum | CCL2 ↑ in AD | [133] |
CXCL12 | AD n = 30 NC n = 30 | Serum | CXCL12 ↓ in AD | [104] |
Progranulin | Mut AD n = 130 NC n = 85 | CSF | Progranulin ↑ in Mut AD | [108] |
Progranulin | Cohort UCSF-MAC AD n = 186 MCI n = 118 NC n = 204 Cohort AddNeuroMedd AD n = 40 MCI n = 66 NC n = 95 Cohort ADNI AD n = 40 MCI n = 159 NC n = 240 | Plasma CSF | No change in plasma progranulin Progranulin ↓ in CSF of AD patients | [109] |
YKL-40 | n = 318 cognitively healthy people at risk of Alzheimer's disease | Plasma | The concentration of YKL-40 ↑ with age, there was a negative association with the deposition of Aβ in the brain | [112] |
sVCAM-1 | AD n = 60 VaD n = 80 Non-dementia n = 40 NC n = 30 | Plasma | sVCAM-1 ↑ in AD, vascular dementia and cerebrovascular disease without dementia (non-dementia) | [115] |
sICAM-1 | AD n = 25 NINDs n = 54 NC n = 15 | Serum | sICAM-1 ↑ in AD and NINDs | [116] |
IL-33 sST2 | AD n = 30 MCI n = 30 NC n = 30 | CSF Serum | IL-33 ↓ in CSF of AD and MCI patients IL-33 ↓ in serum of AD and MCI patients sST2 ↑ in serum of AD and MCI patients | [119] |
EGF | Presymptomatic AD n = 259 | Plasma | EGF ↓ in patients developing AD | [122] |
EGF | AD n = 112 Parkinson's disease n = 236 MCI n = 396 NC n = 56 | Plasma | EGF ↓ AD and MCI | [123] |
Pancreatic polypeptide | AD n = 112 MCI n = 396 NC n = 58 | Plasma | The level of CSF Aβ42 and the ratio of T-tau/Aβ42 correlate with the plasma level of the pancreatic polypeptide | [124] |
HAGH* CASP8* EIF4EBP1* UNC5C* RGMB* JAM-B* TRAIL* SMOC* KYNU* sLDLR* tPA* *—only selected markers with the same change in CSF and plasma are listed for clarity | AD n = 176 MCI n = 131 NC n = 565 | Plasma CSF | HAGH ↑ in AD, CSF and plasma CASP8 ↑ in AD, CSF and plasma EIF4EBP1 ↑ in AD, CSF and plasma UNC5C ↓ in AD, CSF and plasma RGMB ↓ in AD, CSF and plasma JAM-B ↓ in AD, CSF and plasma TRAIL ↓ in AD, CSF and plasma SMOC ↓ in AD, CSF and plasma KYNU ↓ in AD, CSF and plasma sLDLR ↓ in AD, CSF and plasma tPA ↓ in AD, CSF and plasma | [127] |
LYN* CD69* EIF4G1* PLXNA4* SNAP29* FGF-5* MMP-3* KRT19* CSF-1* PAPPA* *—only the top 5 up and downregulated markers are listed for clarity | Discovery cohort: AD n = 106 NC n = 74 Validation cohort: AD n = 36 NC n = 61 | Plasma | LYN ↑ in AD CD69 ↑ in AD EIF4G1 ↑ in AD PLXNA4 ↑ in AD SNAP29 ↑ in AD FGF-5 ↓ in AD MMP-3 ↓ in AD KRT19 ↓ in AD CSF-1 ↓ in AD PAPPA ↓ in AD | [128] |