Table 2.

Comprehensive table of our literature review. Potential biomarkers, type of non-invasive sample used (saliva or buccal cells), experimental techniques, number of participants and the main findings for each separate study are all reported.

Type of Sample	Potential Biomarker	Experimental Technique	Cohort (n)	Main Findings	References
Saliva
	Aβ42	Sandwich ELISA	AD: 15 Healthy controls: 7	Increased	Sabbagh et al. [52]
		Sandwich ELISA	AD: 23 Healthy controls: 31	Increased	McGeer et al. [53]
		Sandwich ELISA	AD: 7 Pre-AD: 3Healthy controls: 26	Increased	Lee et al. [54]
		Sandwich ELISA	AD: 20 Healthy controls: 20	Not detected	Lau et al. [57]
		Sandwich ELISA	AD: 70 Healthy controls: 56	Increased	Bermejo-Pareja et al. [55]
		Nanobead ELISA	AD: 28 Healthy controls: 17	Increased	Kim et al. [56]
		Luminex ELISA	AD: 21 Healthy controls: 38	Not detected	Shi et al. [42]
	Aβ40	Sandwich ELISA	AD: 70 Healthy controls: 56	No change	Bermejo-Pareja et al. [55]
		Nanobead ELISA	AD: 28 Healthy controls: 17	No change	Kim et al. [56]
	T-tau	Sandwich ELISA	AD: 20 Healthy controls: 20	No change	Lau et al. [57]
		Luminex ELISA	AD: 21 Healthy controls: 38	No change	Shi et al. [42]
		SIMOA	AD: 53 MCI: 68 Healthy controls: 160	No change	Ashton et al. [58]
	P-tau	Sandwich ELISA	AD: 20 Healthy controls: 20	No change	Lau et al. [57]
		Luminex ELISA	AD: 21 Healthy controls: 38	No change	Shi et al. [42]
	P-tau/T-tau	Luminex ELISA	AD: 21 Healthy controls: 38	Increased	Shi et al. [42]
		Western blot	AD: 87 MCI: 55 Healthy controls: 167 (used in two consequent studies)	Increased	Pekeles et al. [59]
	Lactoferrin	Mass spectrometry and sandwich ELISA	AD: 116 MCI: 59 Healthy controls: 131 (used in two studies: discovery and validation)	Decreased	Carro et al. [60]
	Acetylcholinesterase	Ellman’s colorimetric method	AD: 36 Healthy controls: 11	Decreased	Sayer et al. [61]
		Ellman’s colorimetric method	AD: 15 Healthy controls: 13	No change	Boston et al. [62]
		Ellman’s colorimetric method	AD: 15 Healthy controls: 15	No change	Bakhtiari et al. [63]
	Oral Microbiome (Porphyromonas Gingivalis)	qPCR	AD: 10	Detection of P. Gingivalis DNA in 10/10 saliva samples	Dominy et al. [26]
	Oral Microbiome	16S rRNA sequencing	AD: 39 Healthy controls: 39	Significantly lower richness and diversity of microbiota detected in AD than healthy controls. Relative abundance of Moraxella, Leptotrichia and Sphaerochaeta in the saliva of AD was greatly increased, whereas that of Rothia was significantly reduced	Liu et al. [64]
	Metabolites: trehalose	EG-IDFET biosensor	AD: 20 Healthy controls: 20	Increased	Lau et al. [57]
	Metabolites: multiple marker panel	LC-MS	AD: 29 MCI: 35 Healthy controls: 45 (used in two studies: discovery and validation)	High diagnostic accuracies (sensitivity: 71–100% and specificity: 80–100%)	Huan et al. [65]
	Metabolites: multiple marker panel	FUPLC-MS	AD: 256 Healthy controls: 218	High diagnostic accuracies (sensitivity: 82–99% and specificity: 91–98%)	Liang et al. [66]
	Metabolites: multiple marker panel	NMR spectroscopy	AD: 9 MCI: 8 Healthy controls: 12	High diagnostic accuracies (sensitivity: 91% and specificity: 84%)	Yilmaz et al. [67]
	Oxidative stress markers (protein carbonyl levels)	ELISA	AD: 15 MCI: 21 Healthy controls: 30	No change	Su et al. [68]
	Salivary flow, antioxidants and oxidative damage products	Total protein content, colorimetry, fluorimetry	AD: 24 Healthy controls: 80	Decreased salivary flow; increased total protein concentration; decreased antioxidant properties; increased levels of oxidative damage to DNA, protein and lipids	Choromanska et al. [69]
Buccal cells	Cytological & cytometric analysis	Microscopic analysis	AD: 29 Healthy controls: 30	No changes in the cytoplasmic and nuclear volumes	Ozlece et al. [70]
	Imaging of telomeres	3D telomeric analysis	AD: 41 Healthy controls: 41	Significantly different 3D telomere profiles. Increased telomere number and aggregation and decrease in telomere length differentiated from normal to severe AD	Mathur et al. [71]
	Altered cytological parameters	Automated laser-scanning cytometry	AD: 13 MCI: 13 Healthy controls: 26	Increased DNA content. Increased abnormal nuclear shape. Decreased neutral lipid content in MCI	Francois et al. [72]
	Multiparameter analysis	Automated laser-scanning cytometry	AD: 20 MCI: 20 Healthy controls: 20	No change in DNA content, aneuploidy, neutral lipids, tau. Lower tau in basal and karyolytic cells versus differentiated cells. Increased Aβ	Francois et al. [73]
	Buccal micronucleus cytome markers	Buccal cytome assay	AD: 54 Healthy controls: 26	Decreased frequencies of basal, condensed chromatin and karyorrhectic cells	Thomas et al. [74]
	Incidence of chromosome 17 & 21 aneuploidy	FISH & fluorescently labeled DNA probes	AD: 54 Healthy controls: 56	Increased	Thomas et al. [75]
	Telomere length	Real time PCR	AD: 54 Healthy controls: 56	Decreased	Thomas et al. [76]
	T-tau	Western blot ELISA	AD: 34 Healthy controls: 67	Increased. Correlated with observed increase in CSF	Hattori et al. [77]
	DNA structure	Super-resolution microscopy	AD: 37 Healthy controls: 37	Increase of the measured DNA-free/poor spaces (i.e., increase in interchromatin compartment)	Garcia et al. [78]

Abbreviations: AD: Alzheimer’s disease; Aβ: amyloid beta; CSF: cerebrospinal fluid; EG-ISFET: extended gate ion-sensitive field-effect transistor; ELISA: enzyme-linked immunosorbent assay; FISH: fluorescent in situ hybridization; FUPLC-MS: faster ultra-performance liquid; chromatography-mass spectrometry; NMR: nuclear magnetic resonance; LC-MS: liquid chromatography-mass spectrometry; MCI: mild cognitive impairment; qPCR; quantitative polymerase chain reaction; rRNA: ribosomal RNA; SIMOA: single molecule array.