Zum Stellenwert der Liquoruntersuchung für die Diagnose demenzieller Erkrankungen

Zusammenfassung

Die Diagnose und Differenzialdiagnose demenzieller Syndrome stellt eine wichtige Herausforderung in der Neurologie dar. Eine komplette Demenzabklärung ist aufwändig und oft nur an Spezialabteilungen verfügbar. Dagegen stellt die Liquoruntersuchung eine billige und gut verfügbare Methode dar. Die vorliegende Übersichtsarbeit sichtet die Aussagekraft und Qualität von Studien, die den Wert der Bestimmung von Tau-Protein (Tau) und Amyloid-β-1 - 42 (Aβ42) im Liquor für die Demenzdiagnostik untersuchten. Beide Proteine haben einen direkten Bezug zum pathogenen Prozess im Gehirn und sind bei der Demenz vom Alzheimer-Typ (DAT) meist deutlich erhöht (Tau) bzw. erniedrigt (Aβ42). Eine Literaturanalyse zeigt, dass Aβ42 und Tau die Diagnose DAT bestätigen und Demenzpatienten von normal alternden Personen gut trennen kann. Vor allem mit einer kombinierten Erfassung beider Werte können hohe Sensitivitäts- und Spezifitätswerte erreicht werden. Die Liquoruntersuchung ermöglicht ferner in vielen Fällen eine prognostische Aussage zur Entwicklung des Mild Cognitive Impairment (MCI) sowie eine Abgrenzung der DAT von extrapyramidalen Erkrankungen, einer Depression oder anderen psychiatrischen Erkrankungen. Weit weniger verlässlich gelingt die Abgrenzung einer DAT von der frontotemporalen (FTD) oder vaskulären (VaD) Demenz. Einige methodische Probleme sind derzeit ungelöst. So werden Kopathologien und Mischdemenzformen nicht hinreichend berücksichtigt. Auch differieren die diagnostischen Kriterien und Fallzahlen der zitierten Arbeiten erheblich. Der Aussagewert der Untersuchung bei Mischdemenzen ist ebenso unbestimmt wie ihr Wert bei Subtypen der DAT. Nach der derzeit vorliegenden Datenlage ist der diagnostische Wert der Bestimmung von Aβ42 und Tau im Liquor als Biomarker für die Demenzdiagnostik nur in einigen Bereichen zielführend.

Abstract

The diagnosis and differential diagnosis of dementia remains an important challenge in neurology and psychiatry. Comprehensive diagnostic investigations are expensive and limited to expert academic centers, whereas cerebrospinal fluid (CSF) examinations are cheap and easily available. The present paper critically reviews recent original articles who have investigated the value of tau and Aβ42 in CSF as biomarkers of dementia. Both proteins are directly related to the pathogenic process in the brain; tau is significantly elevated, whereas Aβ42 is markedly reduced in the CSF of patients with Alzheimer's disease (DAT). Most studies have shown that CSF levels of Aβ42 and tau are well able to confirm the diagnosis of DAT and to separate between dementia patients and normal aging subjects. When analyzed in combination, diagnostic sensitivity and specificity reach reasonably high levels. Furthermore, tau and Aβ42 levels may help to establish a prognosis in mild cognitive impairment (MCI), and have the potential to differentiate between DAT and extrapyramidal diseases, depression and other psychiatric disorders. The power to differentiate DAT from frontotemporal dementia (FTD) or vascular dementia (VaD) is less satisfactory. This review also shows methodological problems, such as the under-representation of mixed dementias and co-pathologies, the use of variable diagnostic and inclusion criteria, and studies with small case rates. The diagnostic value of tau and Aβ42 is also not well studied in mixed dementia and in subtypes of DAT. Overall, CSF analysis of Aβ42 and tau may add to the accuracy of a DAT diagnosis, but have only limited specificity regarding other dementias.

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