Mapping individual molecular connectomes in Alzheimer's disease

INTRODUCTION: Mapping individual differences is crucial to improve personalized medicine approaches in Alzheimer's disease (AD), which is characterized by strong inter-individual variability in the accumulation patterns of tau and amyloid beta pathology. METHODS: We assess the progression of AD across the disease continuum by building individual molecular connectomes using longitudinal positron emission tomography (PET) data. RESULTS: We demonstrate that these connectomes constitute a unique fingerprint, capable of identifying a single individual from a large group of subjects. Alterations in the connectomes discriminate different diagnostic groups and predict cognitive decline to a higher extent than conventional PET measures. We introduce a novel gene-specific transcription network analysis that linked individual tau and amyloid connectomes to a common transcriptomic profile of apoptosis, with the tau connectome being specifically related to pyrimidine metabolism, and the amyloid connectome to histone acetylation. DISCUSSION: Individual molecular connectome mapping provides a novel and sensitive framework to monitor AD progression.