Assessment of Apolipoprotein E Genotype for beta-amyloid Status Prediction

Background: Apolipoprotein E (ApoE) is the major genetic risk factor for sporadic Alzheimer's Disease (AD). Some studies showed a relationship between ApoE4 genotype and the cerebrospinal fluid (CSF) biomarkers (beta-amyloid42,p-Tau, t-Tau), as well as with cognitive status. In this sense, it could be interesting to develop an approach to establish amyloid status in a minimally invasive way. Methods: The present study assessed the ApoE genotype in different participant groups (mild cognitive impairment due to AD (MCI-AD), mild/moderate dementia due to AD, MCI not due to AD (MCI not AD), other neurological diseases, healthy participants) (n = 342). Results: As expected, the ApoE4 allele was more prevalent in AD patients, characterized by impairment in CSF beta-amyloid42 levels (A beta +), than in the other groups (A beta-). In this sense, ApoE4-carrier subjects showed lower CSF levels for beta-amyloid42 and higher CSF levels for t-Tau and p-Tau. From this, a multivariate model to predict A beta status was developed by means of partial least square analysis (PLS) and predictive variables (ApoE genotype, cognitive score, sex, age). This model showed suitable AUC-ROC 0.792 (95% CI, 0.744-0.840) and predictive negative value (81.6%). Conclusion: ApoE genotype could be useful in detecting CSF beta-amyloid42 impairment associated with early AD development.