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Aß oligomers peak in early clinical stages of Alzheimer´s disease and proceed Tau pathology

2023; Wiley; Volume: 19; Issue: S24 Linguagem: Inglês

10.1002/alz.082907

1552-5279

Lara Blömeke, Fabian Rehn, Victoria Kraemer‐Schulien, Janine Kutzsche, Marlene Pils, Tuyen Bujnicki, Josef Priller, Anja Schneider, Jens Wiltfang, Frank Jessen, Emrah Düzel, Katharina Büerger, Robert Perneczky, Stefan Teipel, Christoph Laske, Annika Spottke, Michael Wagner, Oliver Bannach, Dieter Willbold, Oliver Peters,

Cholinesterase and Neurodegenerative Diseases

Abstract Background Aß oligomers are synaptotoxic and may initiate neurodegeneration in early stages of Alzheimer´s disease (AD). Method 526 patients and controls from the DELCODE cohort were clinically diagnosed and afterwards neurobiologically classified using the ATN‐system. Aß and Tau oligomers were determined using the sFIDA technology. Result Within the AD continuum highest oligomer levels in CSF were detected in amyloid positive SCD and MCI. Aß oligomers outnumber in A+T‐ when compared to normal biomarker profile (A‐T‐) or full‐blown AD pathology (A+T+). APOE ε4 was associated with elevated Aß oligomer levels. No differences in Tau oligomers were found. Conclusion The appearance of Aß oligomers in CSF is an early event within the AD continuum precedeing the maximum of Tau pathology. Targeting Aß oligomers by disease modifying treatment in early disease stages might be crucial and is supposed to have the highest therapeutical potential in AD.