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Fortschr Neurol Psychiatr 2022; 90(07/08): 326-335
DOI: 10.1055/a-1839-6237
Übersichtsarbeit

Blutbasierte Biomarker zur Optimierung der Früh- und Differentialdiagnostik der Alzheimer-Demenz

Blood Based Biomarker for Optimization of Early and Differential Diagnosis of Alzheimer’s Dementia
Niels Hansen
1   Klinik für Psychiatrie und Psychotherapie, Universitätsmedizin, Göttingen, Deutschland.
,
Carolin Rauter
1   Klinik für Psychiatrie und Psychotherapie, Universitätsmedizin, Göttingen, Deutschland.
,
Jens Wiltfang
1   Klinik für Psychiatrie und Psychotherapie, Universitätsmedizin, Göttingen, Deutschland.
2   Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Göttingen, Deutschland.
3   Neurosciences and Signaling Group, Biomedizinisches Institut (iBiMED), Abteilung für medizinische Wissenschaft, Universität Aveiro, Aveiro, Portugal.
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Zusammenfassung

Ziele der Studie Die Demenz bei Alzheimer-Krankheit ist eine globale Herausforderung. Studien weisen auf Blutbiomarker zur Diagnose der Alzheimer-Krankheit als eine minimal invasive, schnellere, kostengünstigere und daher zukunftsträchtige Methode hin. Ziel dieser Übersicht ist es, Studien zu vielversprechenden Biomarkern der Alzheimer-Krankheit darzustellen.

Methodik Für diese Übersichtsarbeit wurden aktuelle Studien zusammengestellt.

Ergebnisse Immunassays mit anschließender Massenspektrometrie und solche mit immunmagnetischer Reduktion sind aussichtsreiche Methoden für die Bestimmung von Amyloid-ß 42 (Aß42) und Amyloid-ß 40 (Aß40) für die Bildung der Ratio von Aß42/Aß40 zur blutbasierten Früh- und Differentialdiagnostik der Alzheimer-Krankheit. Die Amyloid-ß (Aß) Peptide im Blutplasma sind ein potentieller Marker der Aß-Pathologie, da sie mit der Aß-Pathologie im Gehirn korrelieren. Das mittels der Simoa Technologie bestimmte phosphorylierte Tau-Protein 181 (p-tau181), das phosphorylierte Tau Protein 231 (p-tau231) und das phosphorylierte Tau Protein 217 (p-tau217) im Blut sind vielversprechend hinsichtlich einer möglichen Optimierung der Früh- und Differentialdiagnostik der Alzheimer-Krankheit und sind Marker einer Tau-Pathologie im Gehirn. Die Neurofilamente Leichtketten (Nfl) und das saure Gliafaserprotein (GFAP) sind als Zusatzmarker hilfreich, um eine axonale und astrogliale Hirnschädigung bei Alzheimer-Krankheit zu beurteilen. GFAP im Blut könnte vor allem als Zusatzmarker zur Frühdiagnostik und Prädiktion des Verlaufs der Alzheimer-Krankheit sinnvoll sein.

Schlussfolgerungen Blutbasierte Biomarker sind ein wichtiger Schritt in Richtung einer weniger invasiven und kostengünstigeren Diagnostik der Alzheimer-Krankheit. Die Ratio Aß42/Aß40, das p-tau181, das p-tau217, das p-tau231, die Nfl und das GFAP sind vielversprechende Blutbiomarker unter Beachtung der AT(N) Klassifikation der Alzheimer-Krankheit. Hochdurchsatzfähige Methoden sollten in großen Kohorten und Metanalysen evaluiert werden. Zudem sollten Konsensus Kriterien mit einheitlichen Protokollen mit Normwerten zur Messung dieser Biomarker erstellt werden. Die Etablierung der AT(N) Klassifikation der Alzheimer-Krankheit im Blut ist unter Berücksichtigung ethischer Gesichtspunkte sowie des Alzheimer Phänotyps ein wichtiger Baustein für die Implementierung einer minimal-invasiven Präzisionsmedizin.

Abstract

Aim Dementia in Alzheimer´s disease is a global challenge. There is growing evidence that investigating blood biomarkers to diagnose Alzheimer´s disease is a promising fast, minimally invasive, and less costly method. The aim of this study was to review available studies on promising biomarkers for Alzheimer´s disease.

Method The latest studies were collated for this review.

Results Immunoassays followed by mass spectrometry and immunomagnetic reduction were reported to be highly relevant methods for detecting amyloid-ß 42 (Aß42) and amyloid-ß 40 (Aß40) to calculate the Aß42/Aß40 ratio, thereby improving the early diagnosis of Alzheimer´s disease. Amyloid-ß (Aß) peptides in blood plasma were considered as potential markers, as they correlated with the brain’s Aß pathology. Phosphorylated tau protein 181 (p-tau181), phosphorylated tau protein 217 (p-tau217) and phosphorylated tau protein 231 (p-tau231) in blood samples assessed via Simoa technology served as parameters for the early and differential diagnosis of AD, and were markers of tau pathology in the brain. Neurofilament light chain (Nfl) and glial fibrillary acid protein (GFAP) were additional markers possibly facilitating the assessment of axonal and astroglial brain damage in Alzheimer´s disease. GFAP in blood was useful as an additional marker to detect early and to predict the time course of Alzheimer´s disease.

Conclusions Determining blood biomarkers represents less invasive and less costly diagnostics for Alzheimer´s disease. The investigation of blood biomarkers such as the Aß42/Aß40 ratio, p-tau217, p-tau231, Nfl and GFAP have been promising in establishing the AT(N) classification for Alzheimer´s disease. High-throughput methods should be evaluated in large patient cohort studies and via meta-analyses of studies. Consensus criteria with standard protocols for measuring these biomarkers while considering ethical issues and Alzheimer´s phenotype should unify normative values from different laboratories. The AT(N) classification of Alzheimer´s disease in blood would be a key element towards the implementation of minimally-invasive precision medicine.

Schlüsselwörter

Alzheimer Demenz - Blut - Biomarker - Diagnose

Key words

Alzheimer´s dementia - blood - biomarker - diagnosis


Publication History

Received: 01 December 2021

Accepted: 26 April 2022

Article published online:
20 July 2022

© 2022. Thieme. All rights reserved.

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