Nanoscience enables ultrasensitive detection of Alzheimer's biomarker Student: Xu Zhang Christine D. Keating. PNAS 2005, 102, No. 7, 2263 –2264 Jwa-Min Nam, Shad Thaxton, Chad A. Mirkin. Science 2003, 301,

Alzheimer's disease Alzheimer's disease (AD), which afflicts an estimated 16 million people worldwide, is a neurodegenerative dementia characterized by memory loss and cognitive impairment. Symptoms begin with mild cognitive impairment. It’s tough to distinguish from other more benign forms of age-related dementia.

Alzheimer's disease Smaller, soluble oligomers of peptides, referred to as amyloid--derived diffusible ligands (ADDLs), have recently been hypothesized as the causative agent in AD- related memory loss. Support for the role of ADDLs comes from their neurotoxicity, and mouse studies that indicate a reversal of memory loss upon injection of amyloid- antibodies This paper presented an ultrasensitive, nanoparticle-based protein detection strategy termed bio-barcode amplification (BCA) to detect ADDL concentration in the cerebrospinal fluid (CSF).

Bio-barcode Amplification (BCA) Strategy CSF is first exposed to monoclonal anti-ADDL antibodies bound to magnetic microparticles. After ADDL binding, the microparticles are separated with a magnetic field and washed before addition of secondary antibodies bound to DNA:Au nanoparticle conjugates. Unreacted Au nanoparticle conjugates are removed after magnetic separation, then elevated temperature release the barcode DNA for analysis. Each Au nanosphere carries hundreds of identical barcode DNA strands, providing substantial amplification.

Scanometric DNA detection The probe strands are arrayed on a solid support and the detection strand is bound to an Au nanosphere. The selectively assembled Au nanospheres then act as nucleation sites for Ag deposition upon the chemical reduction of Ag+ from solution. The resulting Ag deposits can be quantified by a simple desktop scanner such as is used to scan documents for computer manipulation (hence scanometric)

Advantages Ultrasentivity with built-in signal amplification mechanism. 30 attomolar (30 x M) for protein targets, useful for early diagnosis. Can also be applicable for DNA or RNA diagnosis, or simultaneously multiple monitoring. Rapid diagnosis due to performing the BCA assay in homogeneous suspension. It marks one of the first real applications of nanotechnology, while the vast majority of the countless publications on nanoparticle-based diagnostics are in the proof-of-principle stage.