Mapping individual molecular connectomes in Alzheimer's disease

Area of Science:

• Neuroimaging
• Molecular Biology
• Personalized Medicine

Background:

• Alzheimer's disease (AD) exhibits significant inter-individual variability in tau and amyloid beta pathology accumulation.
• Personalized medicine strategies require precise mapping of these individual differences.

Purpose of the Study:

• To develop and validate individual molecular connectome mapping for monitoring AD progression.
• To assess the utility of molecular connectomes in differentiating diagnostic groups and predicting cognitive decline.

Main Methods:

• Longitudinal positron emission tomography (PET) data was used to construct individual molecular connectomes across the AD continuum.
• Gene-specific transcription network analysis was employed to link connectomic data to transcriptomic profiles.

Main Results:

• Individual molecular connectomes serve as unique identifiers, distinguishing individuals within a cohort.
• Connectome alterations effectively discriminate diagnostic groups and predict cognitive decline surpassing conventional PET measures.
• A common transcriptomic profile of apoptosis was linked to both tau and amyloid connectomes, with specific associations to pyrimidine metabolism (tau) and histone acetylation (amyloid).

Conclusions:

• Individual molecular connectome mapping offers a sensitive and novel framework for tracking Alzheimer's disease progression.
• This methodology enhances the understanding of molecular underpinnings of AD pathology and cognitive decline.