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

Article type: Research Article

Authors: Kaur, Gurjeet^a | Poljak, Anne^{a; b; c} | Braidy, Nady^a | Crawford, John D.^a | Lo, Jessica^a | Sachdev, Perminder S.^{a; d; *}

Affiliations: [a] Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, NSW, Australia | [b] Mark Wainwright Analytical Centre, Bioanalytical Mass Spectrometry Facility, University of New South Wales, Sydney, NSW, Australia | [c] School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia | [d] Neuropsychiatric Institute, Euroa Centre, Prince of Wales Hospital, Sydney, NSW, Australia

Correspondence: [*] Correspondence to: Professor Perminder Sachdev, MD, PhD, Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, UNSW Medicine, UNSW, Sydney, NSW, 2052, Australia. Tel.: +61(2) 9385 7663; Fax: +61(2) 9385 3645; E-mail: [email protected].

Abstract: 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 Aβ42 and tau levels were higher when compared to the EOsAD group as a whole. Prevalence of the APOE ɛ4 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 ɛ4, 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.

Keywords: Amyloid-β₄₂ , APOE ɛ4, APP/PSEN, early onset Alzheimer’s disease, neurodegeneration biomarkers, tau

DOI: 10.3233/JAD-200052

Journal: Journal of Alzheimer's Disease, vol. 75, no. 3, pp. 827-843, 2020