Early diagnosis for Alzheimer’s and Parkinson’s

US scientists have developed a biosensor that could detect the early stages of Alzheimer’s disease (AD) and Parkinson’s disease (PD) by measuring low concentrations of protein aggregates in cerebrospinal fluid (CSF).

Neurodegenerative diseases are challenging to diagnose in the early stages as they have similar symptoms. However, on a cellular level, aggregates of the proteins beta-amyloid and alpha-synuclein have been linked to AD and PD, respectively, and so have been suggested as good biomarkers for each disease. ‘Pre-symptomatic diagnosis is a problem,’ says lead researcher Shalini Prasad from the University of Texas at Dallas. ‘Current diagnostic tests don’t have the level of sensitivity and selectivity to detect protein binding. Our goal was to see if we could do both at ultra-low concentrations.’

The biosensor is made up of a printed circuit board overlaid with a porous alumina membrane. The team attached nanobodies (antibody fragments that are specific either for alpha-synuclein aggregates or beta-amyloid aggregates) inside the membrane’s pores. When they added CSF to the sensor, the aggregates bound to their specific nanobodies, causing a change in capacitance that was proportional to the aggregates’ concentration. Using their sensor, the team measured aggregate levels in CSF samples from people with autopsy-confirmed AD, PD and control samples with no neurodegenerative disease. They found that the sensor could distinguish between the samples based on the protein aggregates present, suggesting that it has potential in the early diagnosis of these diseases.

The biosensor microchip integrated with a nanoporous alumina membrane and a polydimethylsiloxane manifold. The sensor can achieve diagnosis of target analytes in under 15 minutes

The biosensor microchip integrated with a nanoporous alumina membrane and a polydimethylsiloxane manifold. The sensor can achieve diagnosis of target analytes in under 15 minutes

‘This looks like a very promising technological approach to the diagnosis of Alzheimer’s disease and Parkinson’s disease,’ says Seth Love, an expert in nerve cell damage and death in neurological disease at the Dementia Research Centre, University of Bristol, UK. However, he adds that ‘the applicability of the findings to ante-mortem disease remains to be demonstrated. It will be important to assess the utility of this approach for diagnosis of early-stage rather than end-stage disease.’

Prasad’s team is now working on a multiplex detection array that will give even greater resolution in distinguishing between forms of dementia and are hoping to put their technology into use in pre-clinical studies.

To read Helen Potter‘s original article see Chemistry World or read the full paper here:

CSF levels of oligomeric alpha-synuclein and beta-amyloid as biomarkers for neurodegenerative disease
Michael R. Sierks, Gaurav Chatterjee, Claire McGraw, Srinath Kasturirangan, Philip Schulz and Shalini Prasad
Integr. Biol., 2012, Advance Article
DOI: 10.1039/C1IB00018G

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