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Table 5 Summary of circulating SENAs associated with disease state and severity of Alzheimer’s disease in human patients

From: Brain alarm by self-extracellular nucleic acids: from neuroinflammation to neurodegeneration

SENA

Study population

Sample type

RNA/DNA name

Findings

References

miRNA

20 HC

40 AD

40 MCI

Plasma

miR-483-5p

Upregulated in AD and MCI (early stage AD patients) compared to HC, decreased in AD versus MCI

Expression positively correlated with cognitive impairment

[325]

26 sMCI

19 pMCI

Whole blood

miR-146a, miR-181a

Upregulated in patients with MCI who later converted to AD

Expression positively correlated with hippocampal atrophy and disconnections in critical white matter brain regions

[15]

31 HC

30 MCI

25 AD

Plasma

miR-206

Upregulated in AD and MCI compared to HC

Expression positively correlated with cognitive decline in MCI patients over a 4-year longitudinal evaluation

[188]

86 HC

121 AD

Serum

miR-202

Downregulated in AD patients

Expression inversely correlated with cognitive impairment

[86]

32 HC

66 AD

Serum

miR-27a-3p

Downregulated in AD patients

Expression negatively correlated with disease severity

[153]

53 AD

Plasma

miR-342-5p

Expression inversely correlated with cognitive decline over a 2-year follow-up period

[65]

41 HC

116 AD

Plasma

miR-21-5p, miR-126-3p

Upregulated in AD patients

Expression positively correlated with cognitive impairment

[129]

60 HC

110 AD

Serum

miR-331-3p

Downregulated in AD patients

Expression inversely correlated with cognitive impairment and blood levels of pro-inflammatory cytokines

[232]

30 HC

48 AD

Serum

miR-374b-5p

Downregulated in AD patients

Expression negatively correlated with cognitive impairment

[452]

19 HC

42 AD

Plasma-derived extracellular vesicles

let-7 g-5p, miR126-3p, miR142-3p, miR146a-5p, mir223-3p

Expression negatively correlated with disease severity

[4]

45 HC

49 AD

Plasma

miR-146a

Expression positively correlated with cognitive impairment

[249]

120 HC

20 AD

Plasma

miR‐103, miR‐107

Expression inversely correlated with dementia severity

[392]

23 HC

23 AD

Serum

miR-34a, miR-29b, miR-181

Upregulated in AD patients

Expression positively correlated with cognitive impairment

[2]

33 HC

33 AD

Serum

miR‑4722‑5p, miR‑615‑3p

Upregulated in AD patients

Expression positively correlated with cognitive impairment

[235]

106 HC

117 AD

Serum

miR-128

Upregulated in AD patients

Expression positively correlated with cognitive impairment and blood levels of pro-inflammatory cytokines

[457]

18 HC

27 AD

Serum

miR-501-3p

Downregulated in AD patients

Expression negatively correlated with cognitive impairment

[147]

62 HC

118 AD

Serum

CSF

miR-433

Downregulated in AD patients

Expression negatively correlated with cognitive impairment

[396]

93 HC

108 AD

Serum

miR-193a-3p

Downregulated in AD patients

Expression negatively correlated with cognitive impairment

[41]

98 HC

105 AD

Serum

miR-133b

Downregulated in AD patients

Expression negatively correlated with cognitive impairment

[430]

62 HC

84 AD

Serum

miR-223

Downregulated in AD patients

Expression negatively correlated with cognitive impairment

[172]

lncRNA

22 HC

22 AD

Whole blood

BDNF-AS

Upregulated in AD patients

Expression positively correlated with cognitive impairment

[84]

90 HC

90 AD

PBMC

lncRNA-17A

Upregulated in AD patients

Expression positively correlated with cognitive impairment

[448]

32 HC

66 AD

Serum

CSF

NEAT1

Upregulated in AD patients

Expression positively correlated with disease severity

[153]

30 HC

48 AD

Serum

MAGI2-AS3

Upregulated in AD patients

Expression positively correlated with cognitive impairment

[452]

120 HC

120 AD

Plasma

CSF

MALAT1

Downregulated in AD patients

Expression inversely correlated with cognitive impairment

[480]

78 HC

82 AD

Serum

HOTAIR

Upregulated in AD patients

Expression positively correlated with cognitive impairment

[239]

83 HC

108 AD

PBMC

GAS5

Upregulated in AD patients

Expression positively correlated with cognitive impairment and hippocampal atrophy

[49]

36 HC

45 AD

Plasma

BACE1-AS

Upregulated in severely impaired AD patients

Expression positively correlated with cognitive impairment

[116]

circRNA

50 HC

50 AD

20 DLB

40 VaD

Whole blood,

Plasma

circ_0003391

Downregulated in AD, but not other types of dementia, as compared to HC

Expression negatively correlated with cognitive impairment and hippocampal atrophy

[230]

40 HC

80 AD

CSF

circ_0002945 (circ-AXL), circ_0032253 (circ-GPHN)

Upregulated in AD patients

Correlated with elevated AD risk

Expression positively correlated with cognitive impairment

[217]

circ_0030777 (circ-PCCA), circ_0031258 (circ-HAUS4)

Downregulated in AD patients

Correlated with decreased AD risk

Expression inversely correlated with cognitive impairment

cfDNA

9 HC

27 AD

Plasma

CNA

Increased concentration in AD patients

Concentration positively correlated with cognitive impairment

[290]

30 HC

30 AD

CSF

8-OHdG (oxidized cfDNA)

Increased concentration in AD patients

Concentration positively correlated with duration of illness

[166]

49 HC

30 spAD

16 rpAD

CSF

mtDNA

Reduced copy number in spAD patients compared to HC and rpAD

Low content correlates with the earliest pathological markers of the disease, low Aβ and high p-tau, but not with the marker of neuronal damage t-tau

[303]

  1. 8-OHdG: 8-hydroxy-2-deoxyguanosine; AD: Alzheimer’s Disease; BACE1-AS: beta-secretase 1-antisense RNA; BDNF-AS: brain-derived neurotrophic factor-antisense RNA; cfDNA: cell-free DNA; circAXL: circular AXL receptor tyrosine kinase; circGPNH: circular gephyrin; circHAUS4: circular HAUS augmin-like complex subunit 4; circPCCA: circular propionyl-CoA carboxylase subunit alpha; circRNA: circular RNA; CNA: circulating nucleic acid; CSF: cerebrospinal fluid; DLB: dementia with Lewy body; GAS5: growth arrest-specific 5; HC: healthy control; HOTAIR: Hox antisense intergenic RNA; lncRNA: long non-coding RNA; MAGI2-AS3: MAGI2 antisense RNA 3; MALAT1: metastasis associated lung adenocarcinoma transcript 1; MCI: mild cognitive impairment; miRNA: microRNA; mtDNA: mitochondrial DNA; NEAT1: nuclear paraspeckle assembly transcript 1; PBMC: peripheral blood mononuclear cells; pMCI: progressor MCI (subjects who progress to AD); rpAD: rapid progressive AD; SENA: self-extracellular nucleic acid; sMCI: stable MCI (subjects which remain cognitively stable over time); spAD: slow progressive AD; VaD: vascular dementia