Alzheimer's Disease Plasma Biomarkers Distinguish Clinical Diagnostic Groups in Memory Clinic Patients

Michelle Gerards; Ann-Katrin Schild; Dix Meiberth; Ayda Rostamzadeh; Jörg Janne Vehreschild; Sebastian Wingen-Heimann; Wibke Johannis; Pamela Martino Adami; Oezguer A Onur; Alfredo Ramirez; Thomas K Karikari; Nicholas J Ashton; Henrik Zetterberg; Kaj Blennow; Franziska Maier; Frank Jessen

doi:10.1159/000524390

Alzheimer's Disease Plasma Biomarkers Distinguish Clinical Diagnostic Groups in Memory Clinic Patients

Dement Geriatr Cogn Disord. 2022;51(2):182-192. doi: 10.1159/000524390. Epub 2022 May 3.

Authors

Michelle Gerards¹, Ann-Katrin Schild², Dix Meiberth¹, Ayda Rostamzadeh¹, Jörg Janne Vehreschild^{3

4}, Sebastian Wingen-Heimann^{3

5}, Wibke Johannis⁶, Pamela Martino Adami⁷, Oezguer A Onur⁸, Alfredo Ramirez^{7

9

10

11

12}, Thomas K Karikari¹³, Nicholas J Ashton^{13

14

15

16}, Henrik Zetterberg^{13

17

18

19

20}, Kaj Blennow^{13

17}, Franziska Maier¹, Frank Jessen^{1

11

12}

Affiliations

¹ Department of Psychiatry and Psychotherapy, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany.
² Department of Psychiatry and Psychotherapy, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany, mgerard2@smail.uni-koeln.de.
³ Department I for Internal Medicine, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany.
⁴ German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany.
⁵ FOM University of Applied Sciences, Cologne, Germany.
⁶ Institute of Clinical Chemistry, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany.
⁷ Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany.
⁸ Department of Neurology, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany.
⁹ Department of Neurodegenerative Diseases and Geriatric Psychiatry, Medical Faculty, University Hospital Bonn, Bonn, Germany.
¹⁰ Department of Psychiatry & Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, San Antonio, Texas, USA.
¹¹ German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
¹² Cluster of Excellence Cellular Stress Responses in Aging-associated Diseases (CECAD), University of Cologne, Cologne, Germany.
¹³ Department of Psychiatry and Neurochemistry, University of Gothenburg, Gothenburg, Sweden.
¹⁴ Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden.
¹⁵ Department of Old Age Psychiatry, Maurice Wohl Clinical Neuroscience Institute, King's College London, London, UK.
¹⁶ Unit for Dementia at South London & Maudsley, NIHR Biomedical Research Centre for Mental Health & Biomedical Research, London, UK.
¹⁷ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
¹⁸ UK Dementia Research Institute, University College London, London, UK.
¹⁹ Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.
²⁰ Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China.

PMID: 35504263
DOI: 10.1159/000524390

Abstract

Introduction: Several recent research studies show high performance of blood biomarkers to identify Alzheimer's disease also in the pre-dementia mild cognitive impairment (MCI) stage, but data from the routine clinical care memory clinic setting are needed.

Methods: We examined plasma samples of 144 memory clinic patients, including dementia of Alzheimer type (DAT, n = 54), MCI (n = 57), and subjective cognitive decline (SCD, n = 33), who either presented as self-referrals or were referred by general practitioners or neurologists or psychiatrists. The plasma biomarkers, amyloid-beta42 (Aß42), amyloid-beta40 (Aß40), phospho-Tau181 (pTau181), total-tau (tTau), and neurofilament light (NFL), as well as different ratios, were measured using the ultrasensitive single molecule array (Simoa) immunoassay technology. Statistical analysis including Kruskal-Wallis test, linear regression, and receiver operating characteristics analyses was performed.

Results: Of the single markers, we observed statistically significant group effects of pTau181 (H(2) = 34.43, p < 0.001) and NFL (H(2) = 27.66, p < 0.001). All individual group comparisons of pTau181 were significant, while the contrast of SCD versus MCI for NFL was not significant. In addition, the ratios of Aß42/Aß40 (H(2) = 7.50, p = 0.02) and pTau181/Aß42 (H(2) = 25.26, p < 0.001) showed significant group effects with significant difference between all groups for pTau181/Aß42 and an SCD versus MCI difference for Aß42/Aß40. PTau181 showed the highest area under the curve of 0.85 for the discrimination of SCD and DAT with a sensitivity of 80% and a specificity of 79% at a cut-off of 12.2 pg/mL. Age influenced Aß42, Aß40, and NFL concentrations.

Conclusion: Plasma pTau181 and NFL, as well as the ratios Aß42/Aß40 and pTau181/Aß42, are biomarkers, which can differentiate diagnostic groups in a memory clinic setting outside of research studies.

Keywords: Alzheimer’s dementia; Alzheimer’s disease; Biomarkers; Plasma; SIMOA-HD-Analyzer.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease* / diagnosis
Amyloid beta-Peptides
Biomarkers
Cognitive Dysfunction* / diagnosis
Humans
ROC Curve
tau Proteins

Substances

Amyloid beta-Peptides
Biomarkers
tau Proteins

Associated data

DRKS/DRKS00023471

Grants and funding

R01 AG068398/AG/NIA NIH HHS/United States