Chapters authored
Plasma Biomarkers in Alzheimer’s Disease
Biomarker study on dementia has developed widely. In applying biomarkers, there seems to be several utilizations such as presymptomatic- and early-stage detection, differential diagnosis, and evaluation of treatment effect. Currently, most reliable fluid markers are amyloid peptide (Aβ) with microtubule-associated protein tau (TAU) and phosphorylated TAU (P-TAU) detected in cerebrospinal fluid (CSF). Aβ42 correlates with plaque pathology, TAU reflects the intensity of neuroaxonal degeneration, and P-TAU may correlate with neurofibrillary tangle (NFT) pathology. An attenuation of the level of Aβ42 and elevation in the ratio of Aβ42 relative to the shorter major species of Aβ42 peptide with 40 amino acid residues (Aβ40) has been identified as significant events in the early stage of Alzheimer’s disease (AD) pathology. In addition, there is great interest in blood-based markers of AD since blood extraction is much less invasive. Moreover, plasma biomarkers can be measured at relatively low expense once a standard system of measurement is established. Although there is not yet an established or validated diagnostic test for plasma biomarkers, there is great interest in blood-based markers. We will summarize reported biomarkers, describe our novel potential plasma biomarker for AD (annexin A5), offering a strategy for selecting candidates, and show our results and evaluation.
Part of the book: Update on Dementia
MFG-E8, A Novel Biomarker for Alzheimer’s Disease and Its Amyloidotic Feature
Biomarker study on dementia has developed and the most reliable fluid markers are amyloid peptide (Aβ), TAU, and phosphorylated TAU detected in cerebrospinal fluid (CSF). We have focused on novel Alzheimer’s disease (AD) biomarker candidates (annexin A5 and Milk fat globule-EGF factor 8 protein [MFG-E8]), Ca2+ and phospholipid binding properties, which were elevated in the neuronal cell culture medium by Aβ42 treatment. We have previously reported annexin A5 as an AD biomarker. In this chapter, we focused on MFG-E8. An immunohistochemical study using AD mouse model (APP/PS1) brains revealed characteristic distributions of the staining with anti-MFG-E8 antibody. Anti-MFG-E8 antibody staining was detected in the core regions of the anti-Aβ-antibody stained plaques in 20 weeks old and older APP/PS1 mice, while no staining was observed in control (wild mouse) and anti-Aβ-antibody staining was detected outside of it. The volume of the staining was augmented with advancing age. It was further revealed that the MFG-E8 protein changed to amyloidotic features over time from the Congo red spectral peak shift and electron microscopic study in vitro. As the emergence of senile plaque takes a long time, MFG-E8 present in the plaque might be in an amyloidotic form. From these results, MFG-E8 is a novel biomarker candidate for AD.
Part of the book: The Global Burden of Disease and Risk Factors - Understanding and Management [Working title]