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Exosomal miRNA in cerebrospinal fluid as biomarkers for neurodegenerative disease.

Exosomal miRNA in cerebrospinal fluid as biomarkers for neurodegenerative disease.

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SA · Author affiliation · country only

Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia. Electronic address: m.alamri@psau.edu.sa.
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Jeddah, SA · Author affiliation

Department of Pharmaceutical Sciences, Pharmacy Program, Batterjee Medical College, Jeddah 21442, Saudi Arabia.
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Morādābād, IN · Author affiliation

Department of Pharmacology, Teerthanker Mahaveer College of Pharmacy, Teerthanker Mahaveer University, Moradabad, 244001, Uttar Pradesh, India.
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Pimpri, IN · Author affiliation

Dr DY Patil Medical College, Hospital and Research Centre, Pimpri, Pune 411018, India.
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Pune, IN · Author affiliation

Dr DY Patil Medical College, Hospital and Research Centre, Pimpri, Pune 411018, India.
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Original abstract

Cerebrospinal fluid protein biomarkers, such as the Aβ42/Aβ40 ratio, phosphorylated tau, and neurofilament light chain, have significantly advanced the diagnostic process for Alzheimer's disease. Nonetheless, these biomarkers face challenges in effectively distinguishing Alzheimer's disease from frontotemporal dementia or Parkinson's disease from dementia with Lewy bodies. This limitation arises from overlapping protein profiles and the variability inherent in immunoassay techniques. A complementary class of analytes is exosomal microRNAs in cerebrospinal fluid, where these non-coding RNAs are secreted by neurons, astrocytes, and microglia, are resistant to RNase degradation, and have a disease-specific expression pattern. This review critically evaluates the existing evidence of cerebrospinal fluid exosomal miRNAs as diagnostic biomarkers in Alzheimer's disease, frontotemporal dementia, Parkinson's disease, dementia with Lewy bodies, and amyotrophic lateral sclerosis. Exosome isolation techniques and detection platform characteristics were compared using RT-qPCR, droplet digital PCR, and small RNA sequencing. Pre-analytical factors, such as collection protocols, hemolysis contamination, freeze-thaw cycling, and circadian sampling variation, were assessed. miRNA profiling data based on disease stratification, receiver operating characteristic performance of the combinatorial panel, and strategies combining exosomal miRNAs with core cerebrospinal fluid proteins were synthesized. This article brings together disease-specific miRNA signatures, pre-analytical standardization needs, and diagnostic accuracy analyses in a translational model to fill the literature gap and form the basis for developing exosomal miRNA panels for rigorously validated clinical laboratory practice.

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