Can peripheral leukocytes be used as Alzheimer’s disease biomarkers?

Abstract

Alzheimer’s disease (AD) is the leading cause of dementia in elderly populations throughout the world and its incidence is on the rise. Current clinical diagnosis of AD requires intensive examination that includes neuropsychological testing and costly brain imaging techniques, and a definitive diagnosis can only be made upon postmortem neuropathological examination. Additionally, antemortem clinical AD diagnosis is typically administered following onset of cognitive and behavioral symptoms. As these symptoms emerge relatively late in disease progression, therapeutic intervention occurs after significant neurodegeneration, thereby limiting efficacy. The identification of noninvasive diagnostic biomarkers of AD is becoming increasingly important to make diagnosis more widely available to clinics with limited access to neuropsychological testing or state-of-the-art brain imaging, reduce the cost of clinical diagnosis, provide a biological measure to track the course of therapeutic intervention, and most importantly, allow for earlier diagnosis – possibly even during the prodromal phase – with hopes of therapeutic intervention prior to appreciable neurodegeneration. Circulating leukocytes are attractive candidate AD biomarkers as they can be obtained in a minimally invasive manner and are easily analyzed by widely available flow cytometry techniques. In this review, we critically analyze the potential utility of peripheral leukocytes as biological markers for AD.

Keywords::

• autoantibody
• B lymphocyte
• biological marker
• cytokine
• dementia
• dendritic cell
• granulocyte
• immune
• inflammation
• macrophage
• monocyte
• natural killer cell
• polymorphonuclear cell
• T lymphocyte

Financial & competing interests disclosure

Terrence Town is supported by a NIH/National Institute on Aging ‘Pathway to Independence’ grant (5R00AG029726–03) and by Cedars-Sinai Medical Center, Department of Neurosurgery and Department of Biomedical Sciences Faculty start-up funds. Terrence Town is the inaugural holder of the Ben Winters Endowed Chair in Regenerative Medicine. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.