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

Abstract

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. To compare the fluid biomarker patterns in early-onset subtypes of AD; EOsAD and ADAD. 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. In the subset of EOsAD cases without APP, PSEN1/PSEN2 mutations, CSF Aβ42 and tau levels were higher when compared to the EOsAD group as a whole. Prevalence of the APOEɛ4 allele was more elevated in EOsAD relative to controls, and not significantly elevated in ADAD cases. Established CSF biomarkers confirmed quantitative differences between variants of EOAD. EOsAD is enriched with APOEɛ4, 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 ∼4-10% of all AD cases, but the reasons for the early onset remain poorly understood.