Recent advances in Alzheimer disease genetics.

PURPOSE OF REVIEW: Genetics studies provide important insights into Alzheimer disease (AD) etiology and mechanisms. Critical advances have been made recently, mainly thanks to the access to novel techniques and larger studies.

RECENT FINDINGS: In monogenic AD, progress has been made with a better understanding of the mechanisms associated with pathogenic variants and the input of clinical studies in presymptomatic individuals. In complex AD, increasing sample sizes in both DNA chip-based (genome-wide association studies, GWAS) and exome/genome sequencing case-control studies unveiled novel common and rare risk factors, while the understanding of their combined effect starts to suggest the existence of rare families with oligogenic inheritance of early-onset, nonmonogenic, AD.

SUMMARY: Most genetic risk factors with a known consequence designate the aggregation of the Aβ peptide as a core etiological factor in complex AD thus confirming that the research based on monogenic AD - where the amyloid cascade seems more straightforward - is relevant to complex AD as well. Novel mechanistic insights and risk factor studies unveiling novel factors and attempting to combine the effect of common and rare variants will offer promising perspectives for future AD prevention, at least regarding early-onset AD, and probably in case of later onset as well.