On the Biomarkers of Alzheimer's Disease

Nakamura et al. examined the evidence, using a discovery and a validation database, that amyloid-β precursor protein (APP)_669-711/amyloid-β (Aβ)_1-42 and Aβ_1-40/Aβ_1-42 ratios, and composites based on traditional statistics; they concluded that these may be useful as biomarkers of Alzheimer's Disease (AD). We reexamined the same datasets, each of which included cognitively normal individuals (CN), individuals with mild cognitive impairment (MCI) and individuals with AD. We used fractal self-similar analyses and reexamined their data from (1) the Japanese National Center for Geriatrics and Gerontology (NCGG) (discovery database) and (2) the Australian Imaging, Biomarker and Lifestyle Study of Ageing (AIBL) cohort (validation database). Results: Using our methods, the three groups of individuals were found to be self-similar, i.e., they could not be differentiated quantitatively, in contrast to the findings of Nakamura et al. Conclusion: Appropriate biomarkers need further study. Our results suggest that APP_669-711/Aβ_1-42 and Aβ_1-40/Aβ_1-42 ratios and their composites may not be valid biomarkers of AD, when reexamined using fractal methods for comparing biomarkers across populations.