Neurogranin and BACE1 as biomarkers for early detection of Alzheimer’s disease

Abstract

AbstractBackgroundA major goal on Alzheimer’s disease (AD) is to identify the disease in its earliest stages to provide optimal care for patients as soon as possible. Currently, the initial clinical diagnosis of AD is substantiated by the quantitative analysis of amyloid β (Aβ) peptide and Tau protein (Tau) in the cerebrospinal fluid (CSF). However, when AD becomes manifest in mental disturbances, Aβ and Tau levels have already become static. Thus, the identification of biomarkers within the earliest stages of AD are of utmost interest.This study aimed to investigate the postsynaptic proteins neurogranin and beta‐secretase 1 (BACE1) for early discrimination in AD spectrum.MethodWe analyzed the data from DELCODE, a multicenter prospective cohort study. CSF levels of neurogranin and BACE1 were measured using ELISA and compared in participants with unimpaired cognition, subjective cognitive decline (SCD), mild cognitive impairment (MCI), mild AD dementia and first‐degree relatives of patients with AD dementia. To explore differences between earlier groups, we further divided SCD into two groups based on Aβ42/pTau181: Aβ42/pTau181‐SCD, Aβ42/pTau181+SCD. Differences between the groups were analyzed with non‐parametric tests. The significance values of group‐wise comparisons were adjusted by Bonferroni correction for multiple tests.ResultA total of 530 participants were finally enrolled, including 91 healthy controls, 212 SCD (155 Aβ42/pTau181‐SCD, 57 Aβ42/pTau181+SCD), 114 MCI, 67 AD dementia and 46 first‐degree relatives. The comparisons between different groups showed CSF levels of neurogranin and BACE1 were significantly higher in Aβ42/pTau181+SCD (503.08 ± 202.89 pg /ml and 2406.39 ± 613.89 pg /ml, respectively) than those in Aβ42/pTau181‐SCD (330.94 ± 134.02 pg /ml and 1972.19 ± 561.94 pg /ml, respectively, both P < 0.0001). The AD group showed higher neurogranin levels than all other groups except Aβ42/pTau181+SCD (all P < 0.05). Furthermore, the CSF levels of Neurogranin were correlated with baseline MMSE scores (spearman r = ‐ 0.16, P < 0.001).ConclusionThis study reveals that neurogranin and BACE1 provide new perspectives for discriminating AD, which may open up possibilities of new therapeutic targets for AD.