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Background: The key neuropathological feature of Alzheimer disease (AD) is the accumulation of extracellular β-amyloid (Aβ) plaques in the brain which begins long before clinical signs of dementia. Immunotherapies targeting Aβ may prevent Aβ accumulation and slow disease progression. Currently, the Aβ status of patients can only be determined by costly β-amyloid-PET-CT or invasively by lumbar puncture. Hence, novel diagnostic methods allowing screening of β-amyloid pathology are needed to select patients for future early immunotherapy preventing AD progression. Atomic force microscopy (AFM) is a technique, developed at Empa, which can resolve Aβ aggregates on red blood cell (RBC) -surfaces with high resolution. However, AFM analytics have not yet been evaluated in detecting Aβ in patient blood samples.

Objective: The primary objective of this study is to evaluate the clinical utility of AFM based analytics of Aβ-aggregates on RBC to differentiate between Aβ-positive and -negative patients presenting with cognitive decline.

Methods: Blood samples taken from patients undergoing routine work-up at the Memory Clinic, Dept. of Neurology, KSSG are analysed by AFM at Empa to detect Aβ-load. The data are correlated to clinical diagnosis.

Relevance: This study will proof the principle if an early marker of AD can be detected in blood, which would pave the road to a simple and reliable screening blood test for AD in the future.