Früherkennung der Alzheimer-Krankheit mit Biomarkern der Bildgebung oder aus dem Liquor

ZUSAMMENFASSUNG

Seit kurzem ist es möglich, die Alzheimer-Krankheit als die häufigste Ursache demenzieller Syndrome anhand von Biomarkern unabhängig von der klinischen Symptomatik zu diagnostizieren. Gerade die Biomarker, die die Amyloid-Pathologie anzeigen, werden bereits Jahre vor Auftreten der ersten klinischen Symptome positiv; werden zusätzlich die Biomarker der Tau-Pathologie und der Neurodegeneration positiv, erhöht sich die diagnostische Spezifität und die Wahrscheinlichkeit klinischer Verschlechterung im kürzeren Verlauf. Es wird die Güte der Biomarker für die Früherkennung der Alzheimer-Krankheit und für die Prognose des klinischen Verlaufs dargestellt.

Die Alzheimer-Biomarker erlauben die Früherkennung der Alzheimer-Krankheit, bevor sich ein demenzielles Syndrom entwickelt. Damit können Patienten identifiziert werden, bei denen Interventionen zur Verzögerung des Fortschreitens der klinischen Symptomatik und des Verhinderns der Demenz erprobt werden.

ABSTRACT

Just recently, new diagnostic criteria for Alzheimer‘s disease (AD) allow the diagnosis of the disease solely on biomarkers independently from the clinical syndrome. In particular, biomarkers for Amyloid pathology already become abnormal many years before symptom onset. In addition, if biomarkers for Tau and neurodegeneration turn positive, diagnostic specificity and probability deterioration increases substantially. The usefulness of the AD biomarkers for early detection and prognosis will be discussed.

AD biomarkers allow the detection of AD already at the pre-dementia level. This offers the opportunity to identify candidates for disease-modifying treatment options.

Schlüsselwörter

Alzheimer-Krankheit - Demenz - leichte kognitive Störung - Biomarker - Amyloid - Tau - Neurodegeneration - Früherkennung

Key words

Alzheimer‘s disease - dementia - mild cognitive impairment - biomarker - amyloid - tau - neurodegeneration - early detection

• Literatur

• 1 McKhann GM, Knopman DS, Chertkow H. et al The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 2011; 7: 263-269
• 2 Albert MS, DeKosky ST, Dickson D. et al The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 2011; 7: 270-279
• 3 Sperling RA, Aisen PS. et al Toward defining the preclinical stages of Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 2011; 7: 280-292
• 4 Jack CR, Bennett DA, Blennow K. et al NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease. Alzheimers Dement 2018; 14: 535-562
• 5 Bateman RJ, Xiong C, Benzinger TL. et al Clinical and biomarker changes in dominantly inherited Alzheimer’s disease. N Engl J Med 2012; 367: 795-804
• 6 Villemagne VL, Burnham S, Bourgeat P. et al Amyloid beta deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer’s disease: a prospective cohort study. Lancet Neurol 2013; 12: 357-367
• 7 Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 2002; 297: 353-356
• 8 Ikonomovic MD, Klunk WE, Abrahamson EE. et al Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer’s disease. Brain 2008; 131: 1630-1645
• 9 Clark CM, Pontecorvo MJ, Beach TG. et al Cerebral PET with florbetapir compared with neuropathology at autopsy for detection of neuritic amyloid-beta plaques: a prospective cohort study. Lancet Neurol 2012; 11: 669-678
• 10 Frost S, Kanagasingam Y, Sohrabi H. et al Retinal vascular biomarkers for early detection and monitoring of Alzheimer’s disease. Transl Psychiatry 2013; 3: e233
• 11 Drzezga A, Grimmer T, Henriksen G. et al Imaging of Amyloid Plaques and Cerebral Glucose Metabolism in Semantic Dementia and Alzheimer’s Disease. Neuroimage 2008; 39: 619-633
• 12 Ossenkoppele R, Jansen WJ, Rabinovici GD. et al Prevalence of amyloid PET positivity in dementia syndromes: a meta-analysis. Jama 2015; 313: 1939-1949
• 13 Jansen WJ, Ossenkoppele R, Knol DL. et al Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis. Jama 2015; 313: 1924-1938
• 14 Grimmer T, Wutz C, Drzezga A. et al The usefulness of amyloid imaging in predicting the clinical outcome after two years in subjects with mild cognitive impairment. Curr Alzheimer Res 2013; 10: 82-85
• 15 Grimmer T, Wutz C, Alexopoulos P. et al Visual Versus Fully Automated Analyses of 18F-FDG and Amyloid PET for Prediction of Dementia Due to Alzheimer Disease in Mild Cognitive Impairment. J Nucl Med 2016; 57: 204-207
• 16 Deutsche Gesellschaft für Psychiatrie und Psychotherapie, PuND, Deutsche Gesellschaft für Neurologie (DGN) S3-Leitlinie „Demenzen“. Berlin: 2016
• 17 Rabinovici GD, Gatsonis C, Apgar C. et al Association of Amyloid Positron Emission Tomography With Subsequent Change in Clinical Management Among Medicare Beneficiaries With Mild Cognitive Impairment or Dementia. JAMA 2019; 321: 1286-1294
• 18 Pannee J, Portelius E, Minthon L. et al Reference measurement procedure for CSF amyloid beta (Abeta) 1–42 and the CSF Abeta1-42/Abeta1-40 ratio – a cross-validation study against amyloid PET. J Neurochem 2016; 139: 651-658
• 19 Caroli A, Prestia A, Galluzzi S. et al Mild cognitive impairment with suspected nonamyloid pathology (SNAP): Prediction of progression. Neurology 2015; 84: 508-515
• 20 Mattsson N, Insel PS, Landau S. et al Diagnostic accuracy of CSF Ab42 and florbetapir PET for Alzheimer’s disease. Ann Clin Transl Neurol 2014; 1: 534-543
• 21 Grimmer T, Riemenschneider M, Forstl H. et al Beta amyloid in Alzheimer’s disease: increased deposition in brain is reflected in reduced concentration in cerebrospinal fluid. Biol Psychiatry 2009; 65: 927-934
• 22 Ossenkoppele R, Rabinovici GD, Smith R. et al Discriminative Accuracy of [18 F]flortaucipir Positron Emission Tomography for Alzheimer Disease vs Other Neurodegenerative Disorders. JAMA 2018; 320: 1151-1162
• 23 Alexopoulos P, Kriett L, Haller B. et al Limited agreement between biomarkers of neuronal injury at different stages of Alzheimer’s disease. Alzheimers dement 2014; 10: 684-689
• 24 Scheltens P, Leys D, Barkhof F. et al Atrophy of medial temporal lobes on MRI in “probable” Alzheimer’s disease and normal ageing: diagnostic value and neuropsychological correlates. J Neurol Neurosurg Psychiatry 1992; 55: 967-972
• 25 Hedderich DM, Spiro JE, Goldhardt O. et al Increasing Diagnostic Accuracy of Mild Cognitive Impairment due to Alzheimer’s Disease by User-Independent, Web-Based Whole-Brain Volumetry. J Alzheimers Dis 2018; 65: 1459-1467