Association of serum apolipoprotein B with cerebrospinal fluid Alzheimer’s disease biomarkers in patients with subjective cognitive decline

Abstract

Background The preclinical stage of Alzheimer's disease (AD) has become a key target stage for future AD prevention trials. Serum apolipoprotein, an important lipid-related factor, has been found to be involved in the pathogenesis of AD. This study was to examine whether apolipoprotein B (ApoB), apolipoprotein A-1 (ApoA1) or the ratio of ApoB and ApoA1 (ApoB/A1) were associated with early changes of cerebrospinal fluid (CSF) AD biomarkers in elderly adults with subjective cognitive decline.Methods This study included 201 cognitive normal (CN) elderly adults and 101 participants with subjective cognitive decline (SCD) from the Chinese Alzheimer's Biomarker and LifestylE (CABLE) database. The Kruskall-Wallis test and Chisquare test were applied in the intergroup comparisons.Multiple linear regression models were used to examine the cross-sectional associations of serum ApoB, ApoA1 and ApoB/A1 levels with CSF AD-related biomarkers.Results Compared with the control group, SCD participants with significant AD biological characteristics had lower ApoB levels. In the total participants, higher level of serum ApoB was associated with increases in CSF Aβ42 (p = 0.0009) and Aβ42/40 (p = 0.0038) as well as decreases in CSF t-tau/Aβ42 (p < 0.0001) and p-tau/Aβ42 (p < 0.0001), independent of APOEɛ4 status. In the further subgroup analysis, these associations were much more significant in the SCD participants. In addition, higher levels of serum ApoB were also found associated with decreases in CSF t-tau (p = 0.0224), p-tau (p = 0.0086) and Aβ40 (p = 0.0297) in the SCD subgroup. Furthermore, we found that these protective associations between serum ApoB and CSF AD core biomarkers were much more significant in the overweight participants. Results showed no association between ApoA1 and all CSF biomarkers in either total participants or subgroups.Conclusions This study is the first to find protective associations of serum ApoB, but not ApoA1, with CSF AD core biomarkers in elderly adults, and these associations were more significant in SCD individuals. This finding indicated that ApoB may play a protective role in the preclinical stage of AD.Identifying the underlying mechanisms may contribute to the discovery of new pathogenic mechanisms and therapeutic targets. Background 4It has been widely accepted that neuropathological processes associated with Alzheimer's disease (AD) begin a decade or more before the emergence of obvious objective cognitive impairment [1][2][3].Biomarker research proved that levels of cerebrospinal fluid (CSF) β-amyloid 42 (Aβ42), phosphorylated tau (p-tau) and total tau (t-tau) have been significantly abnormal in the preclinical stage of AD [3][4][5]. The 2018 National Institute on Aging and Alzheimer's Association (NIAA) research framework further included the three CSF biomarkers in the ATN framework, reflecting brain amyloidosis (A: Aβ42), tau pathology (T: p-tau) and neurodegeneration (N: t-tau) [6]. All these theories shifted the definition of AD from a syndromic to a biological construct and le...