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Klinisch-validierte molekulare Biomarker neurodegenerativer Demenzerkrankungen

Clinically validated molecular biomarkers of neurodegenerative dementia

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Zusammenfassung

Die liquorbasierte neurochemische Demenzdiagnostik (CSF-NDD) ist zwischenzeitlich auf dem S3-Niveau evidenzbasiert validiert, und sie wird mit spezifischer Indikationsstellung für die verbesserte Früh- und Differenzialdiagnostik der multigenetischen (sporadischen) Alzheimer-Demenz (AD) von den gemeinsamen Demenzleitlinien der neuropsychiatrischen Fachgesellschaften empfohlen. Mittels CSF-NDD ist auch eine prädiktive Diagnostik der drohenden AD bei Hochrisikopatienten im Prodromalstadium der leichten kognitiven Beeinträchtigung („mild cognitive impairment“, MCI) möglich. Da bisher aber keine (sekundär)präventive Therapie der AD zur Verfügung steht, wird der Einsatz der CSF-NDD für die molekular prädiktive Demenzdiagnostik von neuropsychiatrischen Leitlinien nicht empfohlen (http://www.DGPPN.de). Die molekulare Diagnostik der präklinischen AD mittels CSF-NDD und [18F]Amyloid-Positronenemissionstomographie hat allerdings schon jetzt einen hohen Stellenwert innerhalb der klinischen Therapieforschung, da auf diese Weise vielversprechende (sekundär)präventive Therapieansätze im klinischen Modell systematisch untersuchbar werden. Zwischenzeitlich zeichnet sich auch ab, dass die Etablierung einer blutbasierten molekularen Frühdiagnostik der AD mittels Multiplex-Assays wahrscheinlich wird. Bisher konnten vielversprechende Assays jedoch nicht konsistent von unabhängigen Arbeitsgruppen validiert werden und im Gegensatz zur CSF-NDD steht eine blutbasierte Diagnostik neurodegenerativer Demenzen noch nicht zur Verfügung.

Summary

As cerebrospinal fluid-based neurochemical dementia diagnostics (CSF-NDD) has now been validated at the S3 evidence level, the German Association for Psychiatry, Psychotherapy and Psychosomatics (DGPPN) and the German Society for Neurology (DGN) recommend CSF-NDD in the recent joint dementia guidelines for improved early and differential diagnostics of multigenic (sporadic) Alzheimer’s dementia (AD). The CSF-NDD also provides a predictive diagnosis of incipient AD for high-risk patients when they are still in the prodromal stage of mild cognitive impairment (MCI) but as no (secondary) preventive therapy of AD is currently available, the use of CSF-NDD for the predictive molecular diagnosis of AD is not recommended in the neuropsychiatry guidelines (http://www.DGPPN.de). However, molecular diagnostics of preclinical AD by CSF-NDD and/or [18F]-amyloid positron emission tomography (PET) has meanwhile gained high clinical relevance for therapeutic clinical research, as this novel clinical model allows systematic screening for promising (secondary) preventive therapy options. Moreover, it has now become apparent that blood-based neurochemical diagnostics of preclinical and early AD will be possible by means of various formats of multiplex assays. However, so far promising blood assays have not been consistently validated by independent research groups and in contrast to CSF-NDD a blood-based diagnosis of AD is not yet available.

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Interessenkonflikt. J. Wiltfang gibt an, dass kein Interessenkonflikt besteht. Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

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Wiltfang, J. Klinisch-validierte molekulare Biomarker neurodegenerativer Demenzerkrankungen. Nervenarzt 85, 1372–1381 (2014). https://doi.org/10.1007/s00115-014-4086-7

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