Alzheimer disease: modeling an Aβ-centered biological network

Area of Science:

• Genetics
• Neuroscience
• Computational Biology

Background:

• Genetically complex diseases often involve rare variants with significant effects, necessitating advanced analytical methods beyond traditional gene-level analysis.
• The amyloid cascade hypothesis posits that amyloid beta (Aβ) peptide drives Alzheimer's disease (AD) pathology.
• Next-generation sequencing enables genome-wide characterization of rare variants, but gene-level aggregation may lack statistical power.

Purpose of the Study:

• To identify and catalog genes and proteins implicated in the biological network of Alzheimer's disease (AD) related to amyloid beta (Aβ).
• To provide a comprehensive list of AD-associated genes and proteins, classified by cellular function, for use in genetic studies.

Main Methods:

• Manual curation of scientific literature to identify proteins interacting with amyloid beta (Aβ) in its production, clearance, aggregation, or toxicity.
• Classification of identified genes/proteins based on their cellular functions within the AD biological network.

Main Results:

• Identification of 335 genes/proteins involved in the amyloid beta (Aβ) biological network in Alzheimer's disease (AD).
• Categorization of these genes/proteins according to their specific cellular functions.

Conclusions:

• Network-based analyses, focusing on genes involved in Aβ pathways, are valuable complements to classical genetic approaches for complex diseases like AD.
• The curated list of 335 genes/proteins provides a valuable resource for ongoing and future genetic studies in Alzheimer's disease.