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Updated: Apr 3, 2026
Hybrid PET/MRI Imaging of Alzheimer's Disease Based on 18F-AV-1451
Published on: April 18, 2025
Alzheimer's Disease FDG PET Imaging Pattern in an Amyloid-Negative Mild Cognitive Impairment Subject
Solveig Tiepolt1, Marianne Patt1, Karl-Titus Hoffmann2
1Department of Nuclear Medicine, University of Leipzig, Leipzig, Germany.
Abstract:
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.
Insights
The revised Alzheimer's disease (AD) criteria use biomarkers, but conflicting results like neurodegeneration without amyloid deposition can occur. Further research is needed to understand these atypical cases for improved AD diagnosis.
Area of Science:
- Neurology
- Biomarker Research
- Neuroimaging
Background:
- Revised NIA-AA criteria for Alzheimer's disease (AD) and mild cognitive impairment (MCI) utilize amyloid and neurodegeneration biomarkers.
- These biomarkers enhance diagnostic confidence in most patients.
- Conflicting biomarker results present challenges in clinical practice.
Observation:
- A subject diagnosed with MCI underwent comprehensive evaluation including neuropsychological testing, FDG PET/MRI, amyloid PET/MRI, and CSF sampling.
- This individual exhibited negative biomarkers for amyloid-beta (Aβ) deposition.
- [18F]FDG PET imaging revealed AD-typical hypometabolism, indicating neurodegeneration.
Findings:
- The case presented a discordant biomarker profile: negative amyloid markers alongside positive neurodegeneration markers (hypometabolism).
- This suggests a potential 'neurodegeneration-first' pattern in AD pathogenesis, diverging from the typical amyloid cascade hypothesis.
Implications:
- Further research is needed to establish the frequency and clinical relevance of such neurodegeneration-first biomarker constellations.
- Understanding these atypical presentations is crucial for refining AD diagnostic criteria and improving our comprehension of AD pathogenesis.
- This case underscores the complexity of AD diagnosis and the need for continued investigation into diverse biomarker patterns.
