The revised NIA-AA diagnostic criteria for Alzheimer's disease (AD) and mild cognitive impairment (MCI) due to AD make use of amyloid pathology and neurodegeneration biomarkers which increase the diagnostic confidence in the majority of patients. However, in daily praxis, cases with conflicting biomarker constellations occur. A MCI subject underwent neuropsychological testing supplemented by FDG and amyloid PET/MRI as well as CSF sampling. In this subject, the biomarkers of Aβ deposition were negative. [18F]FDG PET, however, showed an AD-typical hypometabolism. Further studies are required to determine frequency and relevance of cases with neurodegeneration-first biomarker constellations to improve our understanding on pathogenesis and diagnosis of AD.