Novel sensor allows the detection of Alzheimer's 17 years in advance

Early detection is key in the treatment of Alzheimer's, but achieving that is not always possible.

Now, a research team at the Ruhr-Universität Bochum has developed a new sensor that is able to identify signs of Alzheimer's disease in the blood up to 17 years before the first clinical symptoms appear, according to a press release by the institution. The device detects the misfolding of the protein biomarker amyloid-betta that causes characteristic deposits in the brain.

A simple blood test to reveal the risk of developing the disease

"Our goal is to determine the risk of developing Alzheimer's dementia at a later stage with a simple blood test even before the toxic plaques can form in the brain, in order to ensure that a therapy can be initiated in time," says Professor Klaus Gerwert, founding director of the Centre for Protein Diagnostics (PRODI) at Ruhr-Universität Bochum.

His team joined forces with a group at the German Cancer Research Centre in Heidelberg (DKFZ) headed by Professor Hermann Brenner.

The researchers analyzed blood plasma taken from participants between 2000 and 2002 and then frozen. At that time, the participants hadn't yet been diagnosed with Alzheimer's disease.

The researchers then selected 68 subjects who had been diagnosed with Alzheimer's disease during the 17-year follow-up and compared them with 240 control subjects without such a diagnosis. They aimed to find out whether signs of Alzheimer's disease could already be found in the blood samples at the beginning of the study.

"Surprisingly, we found that the concentration of glial fibrillary acidic protein (GFAP) can indicate the disease up to 17 years before the clinical phase, even though it does so much less precisely than the immuno-infrared sensor," Gerwert said.

The researchers then combined the amyloid-beta misfolding and GFAP concentration to further increase the accuracy of the test in the symptom-free stage.

Now the team has very ambitious plans for their new device.

An efficient screening method for older people

"We plan to use the misfolding test to establish a screening method for older people and determine their risk of developing Alzheimer's dementia," added Gerwert. "The vision of our newly founded start-up betaSENSE is that the disease can be stopped in a symptom-free stage before irreversible damage occurs." 

The invention has already been patented worldwide, and the researchers think its importance will only grow with time and further medical developments.

"The exact timing of therapeutic intervention will become even more important in the future," predicted Léon Beyer, first author and Ph.D. student in Klaus Gerwert's team. "The success of future drug trials will depend on the study participants being correctly characterized and not yet showing irreversible damage at study entry."

The results of the study were published in the journal Alzheimer's Association.

Abstract:
Blood-based biomarkers for Alzheimer's disease (AD) are urgently needed. Here, four plasma biomarkers were measured at baseline in a community-based cohort followed over 17 years, and the association with clinical AD risk was determined. Amyloid beta (Aβ) misfolding status as a structure-based biomarker as well as phosphorylated tau 181 (P-tau181), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) concentration levels were determined at baseline in heparin plasma from 68 participants who were diagnosed with AD and 240 controls without dementia diagnosis throughout follow-up. Aβ misfolding exhibited high disease prediction accuracy of AD diagnosis within 17 years. Among the concentration markers, GFAP showed the best performance, followed by NfL and P-tau181. The combination of Aβ misfolding and GFAP increased the accuracy. Aβ misfolding and GFAP showed a strong ability to predict clinical AD risk and may be important early AD risk markers. Aβ misfolding illustrated its potential as a prescreening tool for AD risk stratification in older adults.