Early-Onset Alzheimer's Disease: What Is Missing in Research?
Level 5 - mechanism / opinion, no new human data
Narrative review summarizing etiology and research gaps without systematic review or meta-analysis
PubMed 33464407 · doi:10.1007/s11910-020-01090-y
What was done
This narrative review summarizes the current understanding of the etiology, genetics, and clinical translation of early-onset Alzheimer's disease (EOAD; onset before age 65) and outlines key research gaps relative to late-onset Alzheimer's disease.
What was found
EOAD accounts for 5% to 10% of all Alzheimer's disease cases. Known pathogenic mutations in APP, PSEN1, and PSEN2 explain only 10% to 15% of EOAD cases. The remaining cases follow non-Mendelian inheritance patterns likely driven by combinations of common and rare genetic variants, most of which have not yet been identified.
Why it matters
The review highlights that the overwhelming majority of early-onset Alzheimer's cases lack an identified single-gene cause, pointing to an urgent need for deeper genetic mapping to support targeted screening, diagnosis, and therapeutics.
Limits
This is a narrative review without systematic search protocols, inclusion criteria, or quantitative meta-analysis. The abstract does not provide primary clinical data, specific risk estimates for novel variants, or sample sizes from referenced studies.
Cited by
- supports Familial Alzheimer's disease accounts for less than 5% of Alzheimer's cases, and APP mutations represent less than 1% of Alzheimer's disease cases in humans.