Abstract

Alzheimer’s disease is a neurodegenerative condition associated with neurofibrillary tangles and cortical deposition of amyloid plaques. Clinical presentation of the disease involves manifestations such as memory loss, cognitive decline and dementia with some of the earliest reported deficits being episodic memory impairment and olfactory dysfunction. Current diagnostic approaches rely on autopsy characterization of gross brain pathology, or brain imaging of biomarkers late in the disease course. The aim of this literature review is to identify and compare newly emerging and novel CSF, serum and mucosal biomarkers, with the potential of making an earlier clinical diagnosis of Alzheimer’s disease. Utilizing such techniques may allow for earlier therapeutic intervention, reduction of disability and enhancement of quality of life. Literature review and analysis was performed by screening the PubMed database for relevant studies within the past 5 years. All studies showed statistically significant (P < 0.05) differences in testing between AD patients and controls. Two categories of serum biomarkers (redox-reactive antiphospholipid antibodies and microRNAs) and an olfactory mucosal marker (microRNA-206) could discriminate between early AD patients and controls with high sensitivity and specificity. In conclusion, certain studies have shown promising results with high sensitivity and specificity, high discriminative potential for Alzheimer’s disease early in its progression, and statistically significant results in larger study samples. Utilization of such diagnostic techniques should increase the efficacy of making an earlier clinical diagnosis of Alzheimer’s disease.

Highlights

  • A novel biomarker, which is sensitive and specific to the development of Alzheimer’s disease (AD) pathology would be an ideal candidate for the preclinical detection of the disease

  • An ideal biomarker for early AD diagnosis should distinguish between cognitively normal elderly controls and patients with mild cognitive impairment (MCI), with great accuracy, sensitivity and specificity

  • These non-coding, small nucleotide molecules have been found to be differentially regulated in the blood, cerebrospinal fluid (CSF) and even brain tissue of patients with AD.[37]

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Summary

Methods

Key FindingsSerum levels of three exosomal miRNAs (miR135a, miR-193b and miR384) were measured through exosome isolation, Western blotting and qRTPCR analysis.Serum miR-135a levelCompared to controls: Significantly increased in AD (P < 0.05)Significantly increased in MCI (P < 0.05)Serum miR-193b levelSignificantly reduced in AD (P < 0.01)Significantly reduced in MCISerum miR-384 levelCompared to MCI: Significantly higher in AD (P < 0.05). Serum levels of three exosomal miRNAs (miR135a, miR-193b and miR384) were measured through exosome isolation, Western blotting and qRTPCR analysis. Compared to controls: Significantly increased in AD (P < 0.05). Compared to MCI: Significantly higher in AD (P < 0.05)

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