Table 3.
Potential salivary biomarkers associated with Alzheimer’s disease (AD) described in clinical studies.
| Potential. Biomarker |
Cohort (n) | Methods | Results | References |
|---|---|---|---|---|
| A-β42 | AD: 10 with severe AD | ELISA assay | ↑Aβ42 in AD, no significant difference in stages of disease | Lee et al. [43] |
| AD: 15 with mild to moderate AD HS: 8 |
ELISA assay | ↑Aβ42 in AD than in HS (AD patients have a 2.45-fold increase) | Sabbagh et al. [44] | |
| AD: 70 (29 mild, 24 moderate and 17 severe) PD: 51 HS: 56 |
ELISA assay | ↑ Aβ42 in AD than in PD and HS but not statistically significant ↑ Aβ42 in mild and moderate AD ↑ Aβ42 in mild AD vs HS p = 0.043 |
Bermejo-Pareja et al. [45] | |
| AD: 28 HS: 17 |
Antibody-based magnet nanoparticles immunoassay | ↑ Aβ42 in severe AD vs. HS, ↑ Aβ42 in severe AD vs. MCI | Kim et al. [46] | |
| AD: 21 HS: 38 |
Luminex assay | Undetectable | Shi et al. [49] | |
| AD: 23 Low controls: 25 High controls (risk for AD) 6 |
ELISA assay | ↑ Aβ42 in AD compared to high controls and low controls, AD > high controls > low controls | McGeer et al. [47] | |
| A-β40 | 70 AD (29 mild, 24 moderate and 17 severe) PD: 51 HS: 56 |
ELISA assay | Unchanged expression between AD, PD, and HS group | Bermejo-Pareja et al. [45] |
| t-TAU | AD: 21 HS: 38 |
Luminex assay | Trend for ↓ t-TAU in AD compared to HS | Shi et al. [49] |
| p-TAU | AD: 21 HS: 38 |
Luminex assay | Trend for ↑ p-TAU in AD compared to HS | Shi et al. [49] |
| p-TAU/t-TAU ratio | AD: 21 HS: 38 |
Luminex assay | ↑significantly in AD | Shi et al. [49] |
| AD: 46 MCI: 55 HS: 47 |
Western Blot analysis | ↑significantly in t-TAU/p-TAU ratio in AD vs. MCI and HS | Pekeles et al. [50] | |
| Lactoferrin | AD: 80 MCI (amnestic MCI): 44 PD: 59 HS: 80 |
ELISA assay | ↓ lactoferrin in AD and MCI compared to HS ↑ lactoferrin in PD compared to HS |
Caro et al [17] |
| 1 cohort: 116 MCI-PET+: 21 AD dementia: 25 FTD -PET: 18 HS: 52 (4 PET+, 48 PET-) 2 cohort: 142 HS (cognitively normal): 74 (4 PET+ and 70 PET-) MCI: 68 (39 MCI-PET+ due to AD, 29 MCI-PET- not due to AD) |
ELISA assay | ↓ lactoferrin in MCI-PET+ and AD compared to HS and FTD ↓ lactoferrin in MCI-PET+ compared to HS and MCI-PET- No differences between HS and MCI-PET- ↑ lactoferrin in the PET- group compared to the MCI-PET+ group |
González-Sánchez et al. [51] | |
| Acetylcholinesterase (AChE) | AD: 15 HS: 15 |
Ellman colorimetric method | ↓ AChE in AD vs. HC, no significant difference in enzymatic activity, no correlation between AChE, age, disease progression | Bakhtiari et al. [53] |
| AD: 30 HS: 30 |
Ellman colorimetric method | ↑ AChE and and PChE in AD | Ahmadi-Motamayel et al. [54] | |
| AD: 15 HS: 13 VD: 13 |
Ellman colorimetric method | ↓ AChE in AD | Boston et al. [55] | |
| AD: 36 (22 responders to AChE-1; 14 non-responders) HS: 11 |
Ellman colorimetric method | ↓ AChE in non-responders vs. responders | Sayer et al. [56] | |
| MCI due to AD: 17 Mild to moderate dementia AD: 14 HS: 12 |
Chromatography mass spectrometry | ↓ significantly myo-inositol and creatine levels in AD vs. HS, AChE ↑ in AD, no differences in taurine, aspartic acid, glutamic acid, glutamine, GABA, N-Acetyl-L-aspartic acid, acetonitrile | Peña-Bautista et al. [57] | |
| Oxidative stress markers | Dementia: 80 (moderate stage) HC: 80 |
Redox assay, antioxidant assay (spectrophotometry method) | ↓ salivary uric acid, catalase, peroxidase in dementia, ↑ TOS and OSI in dementia, ↑ salivary levels of DNA products, protein and lipid oxidative damage | Choromanska et al. [58] |
| Dementia: 50 (AD-dementia: 15; VD: 19; mixed dementia: 16) HS: 50 |
Redox assay, antioxidant assay (spectrophotometry method) | ↓ in superoxide dismutase, catalase, glutathione peroxidase activity in patients with dementia, ↓ glutathione salivary levels (GSH) in patients with severe dementia | Klimiuk et al. [59] | |
| Saliva metabolomics | AD: 256 HS: 218 |
Fast ultra-HPLC coupled with TOF-MS | ↑ sphinganine-1-phosphate, ornithine, phenyl lactic acid in AD patients compared to HS ↓ inosine, 3-dehydrocarnitine, hypoxanthine in AD patients compared to HS |
Liang et al. [60] |
| Discovery Phase group: MCI: 25, HS: 35, AD: 22 Validation Phase group: MCI: 10, HS: 10, AD: 7 |
Differential chemical isotope labelling liquid chromatography mass spectrometry | Statistically significant difference in methylguanosine, histidylphenylalanine, cholinecytidine, phenylalanyproline between AD and HS, difference between phenylalanylproline and alanylphenylalanine between AD and MCI | Huan et al. [62] | |
| AD: 20 PD: 20 HS: 20 |
ELISA assay | ↑ trehalose in AD vs. HS (not significant) | Lau et al. [63] |
↑: increasing; ↓: decreasing; VD: AD subgroup with vascular dementia; TOS: total oxidant status; OSI: oxidative stress index.