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Alzheimer's disease (AD) is a progressive mental disorder disease, which affects 26.6 million people worldwide and estimated increments can be 100 millions by 2050. Since there is no cure at present, early diagnosis of AD is crucial for the current drug treatments. Driven by the need, here we demonstrate for the first time that monoclonal anti-tau antibody-coated gold nanoparticle based two-photon scattering assay can be used for the detection of Alzheimer's tau protein in the 1 pg/mL level which is about 2 orders of magnitude lower than cutoff values (195 pg/mL) for tau protein in CSF (cerebrospinal fluid). We have shown that when anti-tau antibody-coated gold nanoparticles were mixed with 20 ng/mL of tau protein, two-photon Rayleigh scattering intensity (TPRS) increases by about 16 times. The mechanism of TPRS intensity change has been discussed. Our data demonstrated that our TPRS assay is highly sensitive to tau protein and it can distinguish from BSA, which is one of the most abundant protein components in CSF. Our results demonstrate the potential for a broad application of this type of nanobionanotechnology in practical biomedical applications.

Ultrasensitive and Highly Selective Detection of Alzheimer’s Disease Biomarker Using Two-Photon Rayleigh Scattering Properties of Gold Nanoparticle