The Role of Exosomal microRNAs and Oxidative Stress in Neurodegenerative Diseases

Table 1

Exosomal miRNAs as candidate biomarkers for neurodegenerative diseases.

NDDs	Study groups^††	Exosome source	RNA extraction	RNA identification	Exosomal miRNAs	Dysregulation	Efficiency of diagnosis	Ref.
AD	43 MCI; 51 DAT pts; number of NCs is not specified	Serum, plasma, and CSF	Total Exosome RNA Isolation kit	TaqMan qPCR method	miR-193b	DAT<MCI<NCs	/	[103]
	17 young-onset AD^†; 12 NCs	CSF	miRCURY RNA Isolation Kit	RT-qPCR	miR-125b-5p	Upregulated		[104]
					miR-16-5p, miR-451a, and miR-605-5p	Downregulated	, 0.951, and 0.706, respectively
	13 late-onset AD^†; 12 NCs	CSF	miRCURY RNA Isolation Kit	RT-qPCR	miR-125b-5p	Upregulated		[104]
					miR-451a and miR-605-5p		and 0.765, respectively
	208 probable AD (101 MCI and 107 DAT) pts; 228 NCs	Serum	miRcute miRNA isolation kits	RT-qPCR	miR-135a and miR-384	Upregulated	3-miRNA signature: (for MCI)	[105]
					miR-193b	Downregulated
	35 pts; 35 NCs	Plasma	Differential centrifugation	Illumina deep sequencing	miR-185-5p, miR-342-3p, miR-141-3p, miR-342-5p, miR-23b-3p, miR-338-3p, and miR-3613-3p	Downregulated	83–89% accuracy	[106]
	19 pts; 44 NCs	CSF	Traditional TRIzol reagent	Small RNA sequencing	miR-27a-3p, miR-30a-5p, miR-34c-3p, piR_019949, and piR_020364	Upregulated	6-miRNA signature:	[107]
					piR_019324	Downregulated
	10 pts; 10 NCs	CSF	miRCURY Exosome Isolation Kit	RT-qPCR	miR-9-5p and miR-598	Not significantly upregulated	/	[108]
	16 pts; 36 NCs	Serum	Plasma/Serum Exosomal RNA Isolation Kit	Small RNA deep sequencing and RT-qPCR validation	miR-361-5p, miR-30e-5p, miR-93-5p, miR-15a-5p, miR-143-3p, miR-335-5p, miR-106b-5p, miR-101-3p, miR-424-5p, miR-106a-5p, miR-18b-5p, miR-3065-5p, miR-20a-5p, and miR-582-5p	Upregulated	%, % (adding established risk factors to the panel of deregulated miRNA)	[109]
					miR-1306-5p, miR-342-3p, and miR-15b-3p	Downregulated
	5 AD pts; 5 vascular dementia controls	Serum	miRNeasy Mini Kit	TaqMan RT-PCR	miR-34b	Upregulated	/	[110]
	10 AD pts; 11 DLB controls; 11 NCs	Plasma	miRCURYTM RNA Isolation Kit-biofluids	Next generation sequencing and RT-qPCR	miR-451a and miR-21-5p	Downregulated, compared to DLB controls	and 0.93, respectively	[111]
					miR-451a, miR-21-5p, miR-23a-3p, miR-126-3p, Let-7i-5p, and miR-151a-3p	Downregulated, compared to DLB controls	/
					miR-183-5p, miR-24-3p, and miR-423-5p	Not significantly upregulated, compared to DLB controls and NCs	/
PD	78 pts; NCs	CSF	Qiagen miRNeasy Serum/Plasma Kit	TaqMan Real-Time PCR	miR-153, miR-409-3p, miR-10a-5p, and Let-7g-3p	Upregulated	AUC: miR-153, 0.780; miR-409-3p, 0.970; miR-10a-5p, 0.900; combination of miR-153 and miR-409-3p, 0.990	[112]
					miR-1 and miR-19b-3p	Downregulated	and 0.705, respectively
	109 pts; 40 NCs	Serum	miRNeasy Mini Kit	RT-PCR followed by qPCR	miR-24 and miR-195	Upregulated	and 0.697, respectively	[113]
					miR-19b	Downregulated	, %, %
	52 pts; 48 NCs	Plasma	Exosomal RNA and Protein Extraction kit	RT-qPCR	miR-331-5p	Upregulated		[114]
					miR-505
	5 PD pts; 5 vascular parkinsonism controls	Serum	miRNeasy Mini Kit	TaqMan RT-PCR	miR-29a	Upregulated	/	[110]
ASL	10 pts; 20 NCs	Serum	Traditional TRIzol reagent and Qiagen miRNeasy Mini Kit	RT-qPCR	miR-27a-3p	Downregulated	/	[115]
Dementia (AD and vascular dementia)	32 pts with dementia; 16 NCs	Serum	miRcute miRNA isolation kit	RT-qPCR	miR-223	Downregulated		[116]

Risk factors included age, sex, and APOE ε4 allele status; deregulated miRNA panel was exclusive of miR-3065-5p. MiRNAs in this study were derived from unspecified extracellular vesicles. ^†Young-onset AD occurred before the age of 65 years; late-onset AD occurred after the age of 65 years. ^††Only validation cohorts are listed in this table. Abbreviations: AD: Alzheimer’s disease; ALS: amyotrophic lateral sclerosis; AUC: area under the curve; CSF: cerebrospinal fluid; DAT: dementia of Alzheimer type; DLB: dementia with Lewy bodies; MCI: mild cognitive impairment; miR/miRNA: microRNA; NCs: normal controls; NDDs: neurodegenerative diseases; PD: Parkinson’s disease; piR: piwi-interacting RNA; pts: patients; RT-qPCR: quantitative reverse transcription polymerase chain reaction.