Fluid Biomarkers and APOE Status of Early Onset Alzheimer's Disease Variants: A Systematic Review and Meta-Analysis

Background: Numerous studies have reported on cerebrospinal fluid (CSF) and blood biomarkers of Alzheimer's disease (AD); however, to date, none has compared biomarker patterns across the early-onset subtypes, i.e., early onset sporadic AD (EOsAD) and autosomal dominant AD (ADAD), qualitatively and quantitatively. Objective: To compare the fluid biomarker patterns in early-onset subtypes of AD; EOsAD and ADAD. Methods: Six scientific databases were searched for peer-reviewed research publications. The total number of individuals used in all the meta-analysis were 2,427, comprised of 1,337 patients and 1,090 controls. Results: In the subset of EOsAD cases without APP, PSEN1/PSEN2 mutations, CSF A beta(42) and tau levels were higher when compared to the EOsAD group as a whole. Prevalence of the APOE epsilon 4 allele was more elevated in EOsAD relative to controls, and not significantly elevated in ADAD cases. Conclusion: Established CSF biomarkers confirmed quantitative differences between variants of EOAD. EOsAD is enriched with APOE epsilon 4, but the level is not higher than generally reported in late-onset AD. The results prompt further exploration of the etiopathogenesis of EOsAD, which accounts for similar to 4-10% of all AD cases, but the reasons for the early onset remain poorly understood.