Circulating biomarkers for the diagnosis of AD^a.

Sl. no.	Biomarker class	Target biomarkers	Remarks	Specificity (%)	Sensitivity (%)	Sample size	Ref.
1	CSF and blood
	Aβ	Aβ42/40	Decreased significantly, correlates with Aβ positivity	100	84	45	91
		Composite model	Model from Aβ42, 40 and ratio diagnose disease with 90% accuracy	81	96.7	N =121 and N = 252	92
	Tau	t-tau and p-tau	Increased	80	80	97	94
		p-tau-181	Increased, discriminate MCI and AD. Correlates with tau PET positivity, atrophy, and CSF biomarkers	87	92	N1 = 182	95
						N2 = 344
		p-tau-217	Increased 6-fold in AD correlates with Aβ and tau positivity, early diagnosis of AD	91	91	194 + 32	96
		p-tau-231	Increased in the early stage, outperforms p-tau-181, correlates with Aβ and tau deposition	—	—	38 + 313	99
	Protein biomarkers	Neurogranin	Increased in CSF and correlates with CSF biomarkers, atrophy and brain Aβ load	60	79	302	100
		Synaptotagmin	Increased, discriminate MCI and AD	—	—	39 + 78	102
		sTREM	Increased, correlates with CSF Aβ and tau biomarkers, atrophy and brain Aβ load	—	—	155 + 93	103
		YKL-40	Increased, correlates with Aβ deposition and memory deficits	85	85	318	104
		Nf-L	Increased, correlates with CSF t-tau and p-tau, cortical atrophy, Aβ deposition and brain metabolism. Discriminate MCI and AD cases			CSF-187	106
						Ser-405
						N = 196
	RNA biomarkers	BACE1 lcnRNA miRNA panels	Increased in plasma	61.3	87.5	134	109
			Exosome 7 miRNA panel diagnoses with 89% accuracy (miR-185-5p, miR-342-3p, miR-141-3p, miR342-5p, miR-23b-3p, miR-338-3p and miR-3613-3p)	—	—	70	110
			Plasma 6 miRNA panel (miR-185-5p, miR-342-3p, miR-141-3p, miR342-5p, miR-23b-3p, miR-338-3p and miR-3613-3p)	78	75	50	111
			CSF 6–7 miRNA panel, correlates with CSF biomarkers and the cognitive score	—	—	118	112
	Protein and metabolite panel	Multiple protein panel in blood	18 biomolecule alteration was identified (2 cohorts)	93	85	N1 = 961	113
				85	80	N2 = 170
		3 protein panel	Plasma Aβ42/40, pTau-217 and Nf-L diagnose AD and correlates with cognitive changes	—	—	435	114
		4 protein panel	Blood exosomal GAP43, neurogranin, SNAP25 and synaptotagmin-1 are early diagnosis biomarkers	—	—	320	116
		Spingomyelin metabolites	26 metabolites, diagnose AD with an accuracy of 83.33%	80	86.67	N1 = 44	117
						N2 = 767
						N3 = 207
2	Saliva
	Aβ	Aβ42	Increased and specific to AD over PD	—	—	22	118
	Tau	p-tau/t-tau	Increased	—	—	59	119
		p-tau-396/t-tau	Increased, no correlation with other biomarkers	50	73	148	120
	Lf	Full length Lf	Decreased, outperforms CSF biomarkers. Other studies contradict and changes are inconsistent	100	100	N1 = 274	121
				98.6	100	N2 = 127
3	Urine
	Protein	SPP1, GSN and IGFBP7	Increased, MS techniques were used to screen and confirmed by ELISA	—	—	40	125
4	Tear
	Protein	Lipocalin-1, dermcidin, lysozyme-C and lacritin	Proteins are significantly altered in AD over healthy individuals	77	81	23	124
			Significant increase in the tear total protein and flow rate

^ap-tau: phosphorylated tau and t-tau: total tau.