Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
Mapping individual molecular connectomes in Alzheimer's disease.
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Xu Zhilei, Mijalkov Mite, Sun Jiawei, Chang Yu-Wei, Sala Arianna, Volpe Giovanni, Severino Mario, Veronese Mattia, Garcia-Ptacek Sara, Pereira Joana B, Alzheimer's Disease Neuroimaging Initiative
Аннотация
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.
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.