Diagnosis of Mild Cognitive Impairment and Alzheimer's Disease by the Plasma and Serum Amyloid-beta 42 Assay through Highly Sensitive Peptoid Nanosheet Sensor

摘要

Alzheimer's disease (AD) is the most common neurodegenerative disorder with a continuous pathophysiological process starting from the preclinical and mild cognitive impairment (MCI) phases to the dementia phase. Early diagnosis is prerequisite for the early intervention of AD but meanwhile challenging. Amyloid-beta 1-42 (A beta(42)) plays a crucial part in AD pathology. Positron-emission tomography (PET) imaging of A beta(42) in the brain and the measurement of A beta(42) in the cerebrospinal fluid (CSF) have been adopted for the auxiliary diagnosis of AD, but their widespread clinical application has been limited due to the radiation and the high-cost of PET and the invasive lumbar puncture for collecting CSF. Noninvasive and cost-effective blood-based assay is desirable for the early diagnosis of AD. Here, a label-free assay for the quantification of blood A beta(42) was developed using the high-throughput surface plasmon resonance imaging method with the aid of an antibody-mimetic peptoid nanosheet equipping A beta(42)-recognizing loops. We demonstrated that this nanosheet-based sensor system could distinguish the plasma and sera from normal individuals and patients suffering AD and amnestic MCI with high sensitivity and specificity, preceding the diagnostic performance of the A beta(42)-recognizing molecule and the antibody specific to A beta(42). This work provides a label-free, cost-effective, highly sensitive, and high-throughput blood-based assay for early detection of AD.