Recent advances in Alzheimer disease genetics

Area of Science:

• Genetics and genomics
• Neurodegenerative disease research
• Alzheimer disease (AD) etiology

Background:

• Genetics studies are crucial for understanding Alzheimer disease (AD) mechanisms.
• Recent technological advancements and larger study cohorts have accelerated progress.

Approach:

• Investigated monogenic AD, focusing on pathogenic variants and presymptomatic individuals.
• Analyzed large-scale genome-wide association studies (GWAS) and exome/genome sequencing data for complex AD.
• Explored common and rare genetic risk factors and their combined effects.

Key Points:

• Identified novel common and rare risk factors for complex AD through large-scale genetic studies.
• Observed evidence suggesting oligogenic inheritance in some early-onset, non-monogenic AD cases.
• Confirmed the role of amyloid-beta (Aβ) peptide aggregation as a core etiological factor in complex AD.

Conclusions:

• Research on monogenic AD provides relevant insights into complex AD mechanisms, particularly the amyloid cascade.
• Novel mechanistic insights and combined analysis of common/rare variants offer promising avenues for AD prevention.
• Future research holds potential for preventing early-onset AD and possibly later-onset forms.