Alzheimer's disease destroys brain cells and causes problems with long-term memory loss, among other symptoms. In 2006 there were an estimated 26.6 million people suffering from the disease around the world, but this figure is expected to increase by up to four times by 2050. Unfortunately, there is no cure for Alzheimer's and the disease can only be diagnosed by post-mortem identification of senile plaques and neurofibrillary tangles in brain tissue. These tangles are twisted fibres made of tau protein aggregates in brain cells.

Tau proteins make up the structure of neurones. Scientists have found that the cerebrospinal fluid of patients with Alzheimer's disease contains tau proteins that have a very different structure – they are highly phosphorylated – compared with the structure of the same proteins in healthy people. The proteins tie themselves in knots by binding to each other and measuring the level of these proteins could thus provide a way of diagnosing the disease early on in the lab. This would allow potential sufferers to take drugs that slow the onset of the disease.

The technique developed by Paresh Chandra Ray and colleagues of Jackson State University in Mississippi relies on using monoclonal anti-tau antibodies conjugated with gold nanoparticles to identify Alzheimer's tau proteins through antibody-antigen interactions. When the tau proteins are present, several nanoparticles can bind to each protein to produce nanoparticle aggregates (see top figure). The aggregates are blue in colour, compared with red for the nanoparticles on their own, and this colour change can be detected by analysing the change in intensity of two-photon light scattering from the solution. In this method, two photons are scattered by a structure at the same time when excited with light of a certain wavelength.

The method is highly sensitive and can detect Alzheimer's tau protein in concentrations as small as 1 pg/ml. This is two orders of magnitude better than existing colorimetric techniques, says the Jackson University team.

"Our experimental results open up a new possibility for rapid, easy and reliable diagnosis of Alzheimer's disease biomarkers by measuring the two-photon scattering intensity from antibody modified gold nanosystems," Ray told "Such bioconjugated nanoparticles will emerge as a revolutionary tool for ultrasensitive detection of such disease markers."

The work was published in ACS Nano.