A new paradigm for diagnosis of neurodegenerative diseases: peripheral exosomes of brain origin

Abstract

Neurodegenerative diseases are a heterogeneous group of maladies, characterized by progressive loss of neurons. These diseases involve an intricate pattern of cross-talk between different types of cells to maintain specific signaling pathways. A component of such intercellular cross-talk is the exchange of various types of extracellular vesicles (EVs). Exosomes are a subset of EVs, which are increasingly being known for the role they play in the pathogenesis and progression of neurodegenerative diseases, e.g., synucleinopathies and tauopathies. The ability of the central nervous system exosomes to cross the blood–brain barrier into blood has generated enthusiasm in their study as potential biomarkers. However, the lack of standardized, efficient, and ultra-sensitive methods for the isolation and detection of brain-derived exosomes has hampered the development of effective biomarkers. Exosomes mirror heterogeneous biological changes that occur during the progression of these incurable illnesses, potentially offering a more comprehensive outlook of neurodegenerative disease diagnosis, progression and treatment. In this review, we aim to discuss the challenges and opportunities of peripheral biofluid-based brain-exosomes in the diagnosis and biomarker discovery of Alzheimer’s and Parkinson’s diseases. In the later part, we discuss the traditional and emerging methods used for the isolation of exosomes and compare their advantages and disadvantages in clinical settings.

Neurospecific Molecules Measured in Periphery in Humans: How Do They Correlate with the Brain Levels? A Systematic Review

“…The ability of exosomes from the CNS to readily cross the BBB has generated enthusiasm in their investigation as a potential biomarker source. Exosomes are considered to mirror heterogeneous biological changes that occur during the progression of neuropsychiatric diseases [ 67 ]. Animal and human studies demonstrated an accuracy of several types of exosomes and miRNAs in detecting mild, moderate, and severe traumatic brain injury [ 68 ].…”

The Role of Exosomes as Mediators of Neuroinflammation in the Pathogenesis and Treatment of Alzheimer’s Disease

“…In the CNS, glial cells, stem cells and neuron cells can secrete exosomes ( van Niel et al, 2006 ; Younas et al, 2022 ). Exosomes secreted by these cells under normal or pathological conditions can be isolated from human brain tissue and cerebrospinal fluid ( Cai et al, 2017 ; Verheul et al, 2017 ).…”

The evolving role of extracellular vesicles (exosomes) as biomarkers in traumatic brain injury: Clinical perspectives and therapeutic implications

“…The complex nature of TBI, compounded with inadequate scientific knowledge underpinning disease pathophysiology, poses a challenge to developing accurate diagnostic, prognostic, molecular biomarkers, and effective therapeutic modalities. The quantification of EVs as a biomarker has been investigated in studies using serum and plasma-derived EVs without sample enrichment for specific EV subtypes (Younas et al, 2022 ). The majority of attempts to establish EV-derived biomarkers of TBI have centered on leveraging the presence of traditionally investigated blood-derived proteins inside EVs for diagnosis and evaluating neurological impairments predicting the outcome (Winston et al, 2019 ; Vaughn et al, 2021 ).…”