Amyloid-β protein precursor fragments in urine: potential biomarkers for the early detection of mild cognitive impairment and dementia

Background: Current diagnostic methods have limitations in early prediction of dementia. Objective: Develop an early screening tool to identify persons at high risk of dementia for early intervention. Methods: We examined amyloid-β protein precursor (AβPP) and its fragments in urine from cognitively normal controls (CNs) and patients with mild cognitive impairment (MCI) or Alzheimer's disease (AD)-dementia using western blotting with different antibodies and developed a colloidal gold lateral flow-based qualitative strip. Results: Compared with CNs, the amounts of various AβPP fragments with molecular weights of approximately 14, 28, 56, and 68 kDa in patients were greater. We therefore used the strip to detect urine Aβ-containing AβPP fragments and evaluated its potential in multiple aged cohorts from 11 cities in Jiangsu Province, China (n = 4418); Sichuan Provincial People's Hospital (Chengdu, China; n = 408); and the Australian Imaging, Biomarker and Lifestyle Study (AIBL; n = 367). Unitizing Aβ-binding phagocytosis-promoting peptides, the strips showed increasing positivity (9.5–16.9%) with ageing in the Jiangsu cohort and good clinical performance in the Chengdu cohort (κ = 0.704). Significant differences between CNs and patients were found in the AIBL cohort with negative Aβ-PET, those with the slope of Aβ-PET change <1 centiloid per year, those under 75 years of age, or those with a body mass index of 25–30. Conclusions: Our data indicate the high potential of urine AβPP fragments as biomarkers for MCI and dementia at an early stage and warrant further longitudinal studies.