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sFIDA –an Innovative Method for Diagnosing Alzheimer’s Disease

The biomarker-based sFIDA assay is potentially suitable for early diagnosis of Alzheimer’s

Loss of memory, difficulties concentrating, orientation problems – symptoms like these can indicate the onset of Alzheimer’s dementia. Confirming the disease by clinical diagnosis today involves complex follow-up tests in order to assess cognitive deficits, for example memory loss tests or psychological interviews. However, the reliability and accuracy of these methods are limited and cases of misdiagnosis are not uncommon. In addition, they are only applicable after the symptoms have become apparent in the advanced stages of the disease, thus ruling out any possibility for an early diagnosis.

Dangerous protein aggregates between neurons

Today, we know that Alzheimer’s disease unfolds in the brain over a long period of time before symptoms can be detected. Over the course of many years, aggregates and plaque deposits of the amyloid-beta (Aβ) protein accumulate between nerve cells (neurons). While Aβ is harmless as a solitary molecule or “monomer”, the aggregates are toxic and lead to nerve cell damage and death in the brain. The limitations of today’s diagnostics make it particularly difficult to identify an effective treatment: when potential drugs are tested on patients diagnosed with Alzheimer’s dementia, the damages in the brain may already be irreversible. As the progression of the disease cannot be tracked with sufficient precision, positive effects may also simply go unnoticed.

Researchers have therefore been searching for a measurable biological indicator or “biomarker” for Alzheimer’s disease for quite some time. A team of scientists from Forschungszentrum Jülich and the Heinrich-Heine-University Düsseldorf headed by Prof. Dieter Willbold focused on Aβ oligomers for this purpose. Aβ oligomers are smaller aggregates that have been shown to be particularly harmful to nerve cells. As they are also soluble and diffusible, they can distribute easily throughout tissue. The oligomer concentration in body fluids such as blood or liquor could thus provide the earliest and most direct biomarker for diagnosis.

Analysis of spinal fluid allows conclusions to be drawn

In order to detect even the tiniest amounts of these oligomers, the researchers have developed an assay called sFIDA (surface-based fluorescence intensity distribution analysis). This novel laboratory test consists of a few simple steps: First, samples of spinal fluid are applied to a glass surface that is coated with special “capture antibodies”. The Aβ protein in the sample adheres to these, and monomers and oligomers are immobilized.

To be able to distinguish them from each other, further “detection antibodies” are added which are labelled with red and green fluorescent dyes. As the only binding sites on the monomers are already blocked by the capture antibodies, these labelled probes accumulate exclusively on the oligomers. When the dyes are subsequently caused to fluoresce, the oligomers are easy to identify because they shimmer in red and green.

In this way, even single protein aggregates can be detected without any disturbance from the mass of harmless monomers in the sample. In first studies with sFIDA, the researchers were able to distinguish with surprising clarity between samples from patients with Alzheimer’s disease and those from healthy control persons. In addition, a direct connection was found between the oligomer concentration and the severity of cognitive deficits.

Approach may also be suitable for diagnosing Parkinson’s

To optimize and validate sFIDA for routine application, the Federal Ministry of Education and Research (BMBF) provided the project with funding worth € 1.5 million in 2013. As protein aggregates play a role in many other neurodegenerative diseases, it may also be possible to adapt this method from Alzheimer’s disease to other illnesses. As part of the international SYMPATH project, for example, the scientists at Jülich are currently working on adapting sFIDA for the diagnosis of Parkinson’s disease.

Further Information

Press release: Research for Early Diagnosis of Alzheimer’s (11 Sept. 2013; in German)

Institute of Complex Systems, Structural Biochemistry (ICS-6; in German)

Research at ICS-6 on Alzheimer’s (ICS-6; in German)