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