Precision Medicine: Role of Biomarkers in Early Prediction and Diagnosis of Alzheimer’s Disease

Abstract

Alzheimer's disease (AD), the most common form of dementia in the aged people, is a chronic and irreversible neurodegenerative disorder. Early prediction, intervention, and objective diagnosis are very critical in AD. In this chapter, we will introduce the current progress in the prediction and diagnosis of AD, including recent development in diagnostic criteria, genetic testing, neuroimaging techniques, and neurochemical assays. Focus will be on some new applied methods with more specific examples, that is, cerebrospinal fluid (CSF) and blood proteins and peptides, which might serve as biomarkers for the diagnosis of AD. We will also discuss biomarker-based diagnostic strategies and their practical application.

Bridging the Gap Between Fluid Biomarkers for Alzheimer’s Disease, Model Systems, and Patients

“…However, it is important to note that Aβ oligomers can form intracellularly before being deposited extracellularly, and currently this cannot be detected with existing biomarkers. Moreover, Aβ deposition detected by PET ligands can be seen as early as 15 years prior to onset of AD symptoms ( Figure 2 ; Shen et al, 2018 ). The next stage of biomarker alteration include neuronal injury, shown by increased levels of CSF total tau protein (t-tau) and tau phosphorylated at threonine 181 (p-tau181/p-tau), and brain atrophy revealed by structural MRI, and synaptic loss and neurodegeneration detected by DTI or FDG-PET ( Figures 2 , 3 ; Shen et al, 2018 ).…”

“…Axon terminals: CSF levels of SNAP-25 ( Brinkmalm et al, 2014 ; Sutphen et al, 2018 ) and synaptotagmin ( Öhrfelt et al, 2016 ) have been found at elevated levels in patients with AD or MCI compared with control subjects. Synaptic neurodegeneration can be detected by DTI or FDG-PET ( Shen et al, 2018 ). Dendrites: increased CSF neurogranin is found in MCI and AD patients as compared with healthy controls ( Thorsell et al, 2010 ; De Vos et al, 2015 ).…”

“…Currently, CSF biomarkers are the only variety of fluid markers used for diagnosis of early AD, however, they have proven difficult to implement in the clinic due to their limited accessibility and the invasive nature of CSF collection ( Lee et al, 2019 ). There are three core CSF biomarkers for AD diagnosis; Aβ42, t-tau, and p-tau ( Shen et al, 2018 ). Using a combination of the core AD biomarkers is a better approach compared to using the biomarkers individually, especially for differential diagnosis ( Engelborghs et al, 2008 ).…”

“…For instance, detection of autophagic markers in plasma could serve as an early biomarker for AD ( Cho et al, 2019 ). Blood test sampling is routinely performed in the clinic, it is minimally invasive, cheap and suitable for recurrent measurements ( Shen et al, 2018 ).…”

Targeted metabolomics study of early pathological features in hippocampus of triple transgenic Alzheimer’s disease male mice

“…Alzheimer's disease (AD) is one of the most common neurodegenerative diseases, characterized by memory loss, cognitive decline, and personality and behavioral changes. With emergence of millions of new cases worldwide every year and the rapid increase in aged population, AD has become a serious public health threat with huge economic burden (Robinson et al., 2015; Shen et al, 2018). Extracellular senile plaques formed by the deposits of β‐amyloid (Aβ) and intracellular neurofibrillary tangles (NFTs) formed by tau hyperphosphorylation are the two core neuropathological features of AD.…”