Table 1.

Other than miRNA potential EV biomarkers for ALS.

Biofluid	EV Subpopulation	ALS Patients (n)	Controls (n)	Biomarker Identified	Results in ALS Patients Compared to Controls	Author, Year
Size distribution of EVs
CSF	Leukocyte-derived EVs	40	28 AD 36 HC	Number	Increased	Sproviero et al. (2019) [114]
CSF	EVs	20	9 HC	Number	No variation	Thompson et al. (2020) [116]
Plasma	LEVs and SEVs	30	20 HC	Number Mean size	No variation Increased	Sproviero et al. (2018) [115]
Serum	EVs	15	16 HC	Number Mean size	No variation Decreased	Lo et al. (2021) [117]
Protein biomarkers
CSF	SEVs	18 (ALS) 8 (ALS/FTD)	15 HC	C-terminal, full-length TDP-43 fragments	Increased	Ding et al. (2015) [120]
CSF	SEVs	3	3 iNPH	NIR, NOC2L, PDCD6IP, VCAN	Increased	Hayashi et al. (2020) [121]
				SERPINA3, PTPRZ1, C1QC, CCDC19, MYL6B, MARCO, FCGBP, FOLR1, RELN, CFB, CHMP4A	Decreased
CSF		20	9 HC	BLMH	Increased	Thompson et al. (2020) [116]
Plasma	LEVs	30	20 HC	SOD1, TDP-43, p-TDP-43, FUS	Increased	Sproviero et al. (2018) [115]
Plasma	LEVs	40	39 HC	IL-6	Increased	Chen et al. (2019) [131]
Plasma	SEVs	18	/	TDP-43	Increasing overtime	Chen et al. (2020) [133]
Plasma	EVs	106	36 HC 28 MD 32 SBMA	Hyperphosphorylated TDP-43	Increased	Pasetto et al. (2021) [132]
				HSP90, PPIA	Decreased
Plasma	EVs	3	3 HC	CORO1A	Increased	Zhou et al. (2022) [134]
RNA biomarkers
CSF	LEVs	4	4 HC	CUEDC2 (mRNA)	Increased	Otake et al. (2019) [123]
Plasma	LEVs and SEVs	6	6 HC 6 AD 9 PD 9 FTD	CUL3, HIST3H2A, SRSF11, RAB18, SRSF1, DDX5, TRPS1, NFIA, ARIH1, DHX15, NFIX, TUBB1, NF1, NFIB, HUWE1 (mRNA)	Differed from controls	Sproviero et al. (2022) [142]
Lipid and metabolite signatures
Plasma	LEVs	20	20	Lipids Phenylalanine	Increased Decreased	Morasso et al. (2020) [143]

HC, healthy controls; AD, Alzheimer’s disease; iNPH, idiopathic normal-pressure hydrocephalus; MD, muscular dystrophy; SBMA spinal and bulbar muscular atrophy; PD, Parkinson’s disease; FTD, frontotemporal dementia.