Plasma biomarkers for neurodegenerative disorders: ready for prime time?

Abstract

Purpose of reviewSeveral plasma biomarkers for Alzheimer's disease and related disorders (ADRD) have demonstrated clinical and technical robustness. However, are they ready for clinical implementation? This review critically appraises current evidence for and against the immediate use of plasma biomarkers in clinical care. Recent findingsPlasma biomarkers have significantly improved our understanding of ADRD time-course, risk factors, diagnosis and prognosis. These advances are accelerating the development and in-human testing of therapeutic candidates, and the selection of individuals with subtle biological evidence of disease who fit the criteria for early therapeutic targeting. However, standardized tests and well validated cut-off values are lacking. Moreover, some assays (e.g., plasma Ab methods) have poor robustness to withstand inevitable day-to-day technical variations. Additionally, recent reports suggest that common comorbidities of aging (e.g., kidney disease, diabetes, hypertension) can erroneously affect plasma biomarker levels, clinical utility and generalizability. Furthermore, it is unclear if health disparities can explain reported racial/ethnic differences in biomarker levels and functions. Finally, current clinically approved plasma methods are more expensive than CSF assays, questioning their cost effectiveness.

Presenilin Gene Mutation-associated Psychosis

“…While cerebrospinal fluid AD biomarkers as well as amyloid and tau PET can be utilized to improve diagnostic accuracy in individuals experiencing a first episode of psychosis when concern exists for early-onset AD, the former is impractical, and the latter is frequently unavailable outside of specialized centres. Alternatively, although numerous issues have yet to be fully addressed, plasma AD biomarkers show great promise (including Aβ42/Aβ40 as well as numerous p-tau measures) 49 and have the potential to aid in the identification of presenilin gene variant-associated AD underlying emergent psychotic symptoms.…”

A review on the new age methodologies for early detection of Alzheimer's and Parkinson's disease

“…Aβ plaque formation disrupts neuronal function and is an AD hallmark. Plasma Aβ42/Aβ40 ratio relates to brain Aβ‐pathology and correlates with brain Aβ‐PET scan and CSF Aβ42/Aβ40 ratio 3 . Plasma phosphorylated‐tau (p‐tau181, p‐tau217, p‐tau231) biomarkers predict cognitive decline and also reflect Aβ and tau abnormalities 3 .…”

“…1 AD is a global health crisis. Many AD patients are reported to suffer from mild cognitive impairment (MCI) 3 Increased expression of miR-16-5p, miR-25-3p, miR-92a-3p and miR-451a was found in exosomes isolated from plasma of prodromal AD patients. 4 Decreased expression of miR-137, miR-181c, miR-9, miR-29a, miR-29b, miR-92a-3p and miR-486-5p whereas enhanced expression of miR-29a-3p in serum of preclinical and prodromal AD patients with/ without MCI has been reported.…”

Plasma Biomarkers of Alzheimer’s Disease: A Review of Available Assays, Recent Developments, and Implications for Clinical Practice

“…a costs of equipment implementation not shown; b cost of liquid chromatography with tandem mass spectrometry (LC-MS/MS)-based assay; an approved Lumipulse assay is believed to cost under $500; c projected costs; the PrecivityAD TM test from C2N Diagnostics, for example, still costs $1,250 per analysis. PET, positron emission tomography; A␤, amyloid-beta; CSF, cerebrospinal fluid; IP-MS, immunoprecipitation mass spectrometry [132,[138][139][140][141][142][143].…”