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Mapping individual molecular connectomes in Alzheimer's disease
Zhilei Xu1, Mite Mijalkov1, Jiawei Sun1
1Department of Clinical Neuroscience, Division of Neuro, Karolinska Institutet, Solna, Sweden.
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.
