Table 2.

Exosomes used as potential diagnostic markers for various brain neurodegenerative disorders

Disease	Objective	Activity	Outcome	References
Parkinson’s disease (PD) and Alzheimer’s disease (AD)	MicroRNA profiling method for exosomal miRNAs in the cerebrospinal fluid (CSF)	miRNA profiles of exosomes present in the cerebrospinal fluid of PD and AD patients	Elevated levels of miR-153, miR-409-3p, miR-10a-5p and let-7 g-3p in the CSF	[131]
PD	Investigation of 24 miRNAs as diagnostic tools	Quantitation of serum miRNAs by qRT-PCR	miR-19b, miR-24 and miR-195 acted as biomarkers for Parkinson’s	[132]
AD	Determining the effect of AD on the levels of plasma neuronal exosomes	Quantification of plasma neuron derived exosomes for biomarker properties	Diminished levels of the proteins in dementia due to Alzheimer’s	[121]
AD	Investigation of astrocyte inflammatory mechanisms	Enzyme linked immunosorbent assay quantification of the complement proteins of exosomes from AD patients and controls	Levels of astrocyte-derived exosomes were higher at the dementia stage, and complementary proteins CD59 and CD46 were diminished	[141]
Huntington’s disease (HD)	Delivery of abnormal downregulated miRNAs to normalize gene regulation	Potential of exosome-based delivery of miRNA in HD was analysed	Injection of Exo-124 in mice reduced expression of RE1-silencing transcription factor	[151]
PD and AD	Development of in vivo neuroimaging of exosomes using gold nanoparticles	Tracking of the migration patterns of MSC-derived exosomes	MSC-derived exosomes targeted the pathologically relevant sites in murine models upto 96 h	[146]
AD	Correlation of salivary exosomes with progression of AD	Concentration of salivary exosomes in Alzheimer patients were compared to that of healthy controls	Nanoparticle tracking analysis method revealed differences in salivary exosomes in Alzheimer patients and healthy controls	[59]
PD	Determination of capability of human of umbilical cord MSCs in the treatment of PD	Determination of the ability of human umbilical cord MSC-derived exosomes to offer neuroprotection	Exosomes reduced the loss of dopaminergic neurons in the substantia niagra along with upregulation of dopamine	[133]
PD	Investigation of the effect of long non-coding RNA in blood exosomes in the pathogenesis of Parkinson’s	Evaluation of the levels of lncRNAs in exosomes of PD patients and healthy controls	Long non-coding MKRN2-42:1 revealed positive correlation with UPDRS III score in Parkinson’s subjects	[134]
PD	Assessment of serum neuronal exosomes as biomarkers	Levels of neuron-derived exosomal α-synuclein and clusterin was analysed	Neuron-derived exosomal α-synuclein and clusterin was found to be elevated in PD with AUC = 0.98	[135]
AD	Determination of therapeutic effect of exosomes containing miR-29b in rat model	Investigation of the expression levels of miR-29b in a rat model	Transfected cells displayed overexpression of miR-29 along with downregulation of target genes	[142]
PD	Demonstration of the effect of fibroblast growth factor-2 (FGF2) in the release of exosomes enriched with Rab proteins	Expression levels of Rab8b and Rab31 enriched exosomes due to FGF2 were analysed	Significant upregulation in the levels of exosomes with Rab8b and Rab31 due to FGF2	[137]
AD	Determination of the therapeutic effect of exosomes derived from 3D culture of stem cells	Evaluating the level of regulation of exosomes derived from a 3D culture	Exosomes derived from the 3D culture altered the expression of α-secretase and β-secretase	[143]
AD	Fingerprinting of small RNA content in extracellular vesicles	Analysis of small RNA content in exosomes derived from the frontal cortex	Upregulation of disease-associated miRNA in exosomes derived from the brain	[139]
PD	Proteomic analysis of serum exosomes and identification of biomarkers	Analysis of the protein’s levels of serum exosomes	Reduced expression levels of proteins such as apolipoprotein D and J and afamin in PD patients	[136]
AD	Examining the effect of MSC-derived exosomes in AD mouse model	Effect on recovery of cognitive function in AD mouse model	MSC-derived exosomes alleviated cognitive impairment due to beta amyloid 1–42	[144]
AD	Design of curcumin exosomes to alleviate symptoms of AD	Potential of curcumin exosomes to prevent hyperphosphorylation in AD mice was analysed	Curcumin exosomes caused inhibition of Tau phosphorylation	[140]
Amyotrophic lateral sclerosis (ALS)	Proteomic analysis of CSF exosomes of ALS patients	Identification of proteins that were linked to ALS was conducted	Novel INHAT repressor (NIR) protein levels were diminished in the motor neurons of patients with ALS	[147]
ALS	Amelioration of ALS progression using adipose stem cell–derived exosomes	Determination of the neuroprotective effects of adipose stem cell–derived exosomes	Improvement of motor performance and reduced activation of glial cells	[148]
ALS	Determination of biomarker characteristics of IL-6 in ALS	Analysis of expression levels of IL-6 in ALS patients	Increased levels of IL-6 in astrocyte-derived exosomes of ALS patients	[149]
ALS	Biomarker identification in CSF of ALS patients	Comprehensive analysis of exosomal RNAs in the CSF of ALS patients	CUEDC2 was suggested to a biomarker candidate for ALS	[150]
AD	Examining the effect of exosomes to reduce neuroinflammation in AD	Analysis of the potential of exosomes to diminish amyloid beta deposits and reduce neuroinflammation	Stem cell–derived exosomes were able to eliminate the deposition of Aβ in mice	[145]
PD	Development of a biocompatible method for delivery across the blood–brain barrier	Potential of blood exosomes loaded with dopamine for Parkinson’s therapy	Distribution was enhanced by 15-fold in the brain	[35]