Chapter 7 - Cell-Based Alzheimer’s Disease Biomarkers

Abstract

Currently, there is no simple, minimally invasive, and inexpensive procedure that can diagnose Alzheimer’s disease (AD) with acceptable accuracy, sensitivity, and specificity. Given its multifactorial nature, the diagnosis of sporadic AD is challenging, and early diagnosis is still elusive. Although commonly viewed as a disease of central nervous system, several AD-related abnormalities in metabolic, oxidative, and inflammatory pathways in peripheral cellular systems have been discovered. Cytomic or cell-based AD biomarker approaches involve multiparametric assessment of functional, morphological, and antigenic differences between cells isolated from peripheral systems from individuals with or without AD. The most widely researched peripheral cells for assessment of AD biomarkers include blood cells (lymphocytes, red blood cells, platelets, and leukocytes), skin fibroblasts, retinal nerve cells, and buccal cells. Most cell-based AD biomarkers are manifestations of AD-related dysfunctional cellular and molecular signaling in peripheral systems. Some cell-based AD biomarkers have similar levels of sensitivity and specificity as cerebrospinal fluid (CSF)-based biomarkers, and several have demonstrated the ability to differentiate between AD and non-AD dementia cases, detect early-stage AD, and diagnose autopsy-confirmed AD. Moreover, cell-based AD biomarker assays are simple, inexpensive, and noninvasive or minimally invasive in nature and have the potential to be used not only as preclinical AD biomarkers for research but also for community-based screening, in-office diagnosis, and assessment of treatment efficacy in patients and in the clinical trial setting. However, more validation, standardization, and multicenter developmental studies within large cohorts are necessary before peripheral cell-based AD biomarker tests can be translated to clinical care.