A prognostic Alzheimer's disease blood test in the symptom-free stage
Memory deficit is a normal side effect of aging; at what point does
memory loss become pathological?

Date:
January 6, 2021
Source:
Ruhr-University Bochum
Summary:
Using a blood test, a 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. Using a newly
developed test, they identified all 22 subjects at study entry
who developed Alzheimer's dementia, thus the clinical symptoms,
within six years.



FULL STORY ========================================================================== Memory deficit is a normal side effect of aging. At what point does
memory loss become pathological?

========================================================================== 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-Universita"t 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 (Ab) 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 Ab 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 Ab 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 Ab peptide. "Misfolding of Ab 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
Ab isoforms with a concentration decrease for Ab42 as ratio to Ab40 in
plasma. The Amsterdam group measured Ab 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 Ab and subsequent plaque deposition
of Ab42 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.


========================================================================== Story Source: Materials provided by Ruhr-University_Bochum. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Julia Stockmann, Inge M. W. Verberk, Nina Timmesfeld, Robin Denz,
Brian
Budde, Julia Lange-Leifhelm, Philip Scheltens, Wiesje M. van
der Flier, Andreas Nabers, Charlotte E. Teunissen, Klaus
Gerwert. Amyloid- b misfolding as a plasma biomarker indicates
risk for future clinical Alzheimer's disease in individuals with
subjective cognitive decline.

Alzheimer's Research & Therapy, 2020; 12 (1) DOI:
10.1186/s13195-020- 00738-8 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/01/210106115725.htm

--- up 3 weeks, 1 day, 7 hours, 57 minutes
* Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1337:3/111)