A prognostic Alzheimer's disease blood test in the symptom-free stage

January 06, 2021

Using a blood test, a German-Dutch research team has predicted the risk of Alzheimer's disease in people who were clinically diagnosed as not having Alzheimer's disease but who perceived themselves as cognitively impaired (Subjective Cognitive Declined, SCD). The researchers analyzed blood samples from an SCD cohort supervised at the Alzheimer Center Amsterdam. Using a test developed at Ruhr-Universität Bochum (RUB) called the Immuno-Infrared Sensor, they identified all 22 subjects at study entry who developed Alzheimer's dementia, thus the clinical symptoms, within six years. The test also showed which subjects were at very low risk to develop Alzheimer's dementia within six years. The team describes the results in the journal Alzheimer's Research and Therapy, published online 24 December 2020.

For the study, the team led by biophysics Professor Klaus Gerwert and Julia Stockmann of the Bochum Research Center for Protein Diagnostics (Prodi) collaborated with RUB statistician Professor Nina Timmesfeld, Department of Medical Informatics, Biometry and Epidemiology, and researchers from the Amsterdam University Medical Centers, Location Vrije University (VUmc) led by Professor Charlotte Teunissen and Professor Philip Scheltens.

Sensor detects misfolded proteins in blood

The SCD cohort included 203 individuals. At study entry, blood samples were taken from all the participants and analyzed using the patented immuno-infrared sensor that detects misfolding of the amyloid-beta (Aβ) peptide, which is a biomarker for Alzheimer's disease. In addition, the subjects underwent extensive Alzheimer's disease diagnostic testing; at study entry, this did not provide a diagnosis of Alzheimer's disease in any of the subjects studied. The immuno-infrared sensor, on the other hand, detected misfolded Aβ peptides at study entry in all 22 subjects who developed the clinical disease in the following six years. In subjects who showed mild misfolding, it took on average longer (3.4 years) for conversion to clinical Alzheimer than in subjects with severe Aβ misfolding (2.2 years).

Together with statistician Nina Timmesfeld, the researchers predicted the risk of developing clinical Alzheimer's disease. According to the statistical model, SCD subjects with mild misfolding have an 11-fold higher risk and SCD subjects with severe misfolding have a 19-fold higher risk of developing clinical Alzheimer's in the following six years than subjects without misfolded Aβ peptide. "Misfolding of Aβ is therefore a very precise prognostic plasma biomarker," concludes Klaus Gerwert.

Combination of two biomarkers further improves prognosis

In addition, the team checked whether the combination of two different measurement methods in the plasma biomarker panel could further improve the prediction of disease risk. For this purpose, they combined the misfolding of all Aβ isoforms with a concentration decrease for Aβ42 as ratio to Aβ40 in plasma. The Amsterdam group measured Aβ concentrations using the new single-molecule array (SIMOA) technology. This increased the assay accuracy from an AUC (area under the ROC curve) of 0.94 to 0.99.

"We can now very accurately predict the risk of developing clinical Alzheimer's disease in the future, with a simple blood test on symptom-free individuals with subjective concerns," explains Klaus Gerwert. "However, we can just as confidently give the all-clear for SCD patients who have a very low probability of developing Alzheimer's disease in the next six years."

"Through the plasma biomarker panel, we can monitor disease progression over 14 years, beginning in the asymptomatic state with misfolding of Aβ and subsequent plaque deposition of Aβ42 in the brain associated with the first cognitive impairments," Julia Stockmann adds.

Hope for early-stage treatment

Such a blood test, which can detect the onset of Alzheimer's dementia even in the asymptomatic state, would be particularly useful if an active substance were available to treat the disease. In March 2021, the U.S. Food and Drug Administration will decide whether to approve the drug aducanumab. "Our results indicate that Alzheimer's drugs should be applied as early as possible in a non-clinical stage to improve therapy response," Klaus Gerwert said. The Bochum researcher is promoting the immuno-infrared sensor to be used in the selection of trial participants in the future to achieve a significantly better therapy response.
-end-


Ruhr-University Bochum

Related Dementia Articles from Brightsurf:

The danger of Z-drugs for dementia patients
Strong sleeping pills known as 'Z-drugs' are linked with an increased risk of falls, fractures and stroke among people with dementia, according to new research.

The long road to dementia
Alzheimer's disease develops over decades. It begins with a fatal chain reaction in which masses of misfolded beta-amyloid proteins are produced that in the end literally flood the brain.

Why people with dementia go missing
People with dementia are more likely to go missing in areas where road networks are dense, complicated and disordered - according to new research from the University of East Anglia.

PTSD may double risk of dementia
People who have experienced post-traumatic stress disorder (PTSD) are up to twice as likely to develop dementia later in life, according to a new study by UCL researchers, published in the British Journal of Psychiatry.

Dementia education
School-based dementia education could deliver much needed empathy and understanding for older generations as new research from the University of South Australia shows it can significantly improve dementia knowledge and awareness among younger generations.

Building dementia friendly churches
A project to help church communities become more 'dementia friendly' has had a significant impact across the country.

A "feeling" for dementia?
A research team led by the DZNE concludes that personal perception can be an important indicator for the early detection of Alzheimer's disease.

New biomarker for dementia diagnosis
Medical researchers in the UK and Australia have identified a new marker which could support the search for novel preventative and therapeutic treatments for dementia.

Digital solutions for dementia care
Telehealth delivery of dementia care in the home can be as effective as face-to-face home visit services if carers and recipients take advantage of the technologies available, Australian researchers say.

Despite a marked reduction in the prevalence of dementia, the number of people with dementia is set to double by 2050 according to new Alzheimer Europe report
Today, at a European Parliament lunch debate, Alzheimer Europe launched a new report presenting the findings of its collaborative analysis of recent prevalence studies and setting out updated prevalence rates for dementia in Europe.

Read More: Dementia News and Dementia Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.