Background: Little is known so far about the brain phenotype and the spatial interplay
of different Alzheimer’s disease (AD) biomarkers with structural and functional brain connectivity
in the early phase of autosomal-dominant AD (ADAD). Multimodal PET/MRI might be suitable to
fill this gap.
Material and Methods: We presented a 31-year-old male patient without a family history of dementia
with progressive worsening of memory and motor function. Two separate sessions of 3T
PET/MRI acquisitions were arranged with the ß-amyloid tracer [18F]Florbetaben and the secondgeneration
tau tracer [18F]PI-2620. Simultaneously acquired MRI consisted of high-resolution 3D
T1, diffusion-tensor imaging (DTI), and resting-state fMRI. PET/MRI data were compared with
ten age-matched healthy controls.
Results: Widespread β-amyloid depositions were found in cortical regions, and striatum (Thal
stage III) along with tau pathology restricted to the mesial-temporal structures (Braak stage III/IV).
Volumetric/shape analysis of subcortical structures revealed atrophy of the hippocampal-amygdala
complex. In addition, cortical thinning was detected in the right middle temporal pole. Alterations
of multiple DTI indices were noted in the major white matter fiber bundles, together with disruption
of default mode and sensory-motor network functional connectivity. Molecular genetic analysis
by next-generation sequencing revealed a heterozygote missense pathogenic variant of the
Conclusion : Multimodal PET/MR imaging is able to deliver, in a one-stop-shop approach, an array
of molecular, structural and functional brain information in AD due to de novo pathogenic
variant, which can be studied for spatial interplay and might provide a rationale for initiating anti-
amyloid/tau therapeutic approaches.