Association of serum Apolipoprotein B with cerebrospinal fluid biomarkers of Alzheimer's pathology

Abstract

Objective: To examine whether apolipoprotein B (ApoB), apolipoprotein A-1 (ApoA1), or their ratio (ApoB/A1) were associated with early changes in cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) pathology in elderly adults with subjective cognitive decline (SCD).

Methods: This study included 507 objective cognitive normal participants from the Chinese Alzheimer's Biomarker and LifestylE (CABLE) database including 288 cognitive normal participants (CN) and 219 SCD. Multiple linear regression models were used to examine the associations of apolipoproteins with CSF AD biomarkers.

Results: Compared with control group, SCD participants with significant AD biological characteristics had lower ApoB levels (P = 0.0461). In total participants, lower level of serum ApoB was associated with decreases in CSF Aβ42 (P = 0.0015) and Aβ42/40 (P = 0.0081) as well as increases in CSF p-tau/Aβ42 (P < 0.0001) and t-tau/Aβ42 (P = 0.0013), independent of APOEɛ4 status. In further subgroup analysis, these associations were more significant in SCD participants (ApoB × Diagnose: P < 0.05). In addition, lower levels of ApoB were also found associated with increases in p-tau in the SCD subgroup (P = 0.0263). Furthermore, these protective associations were more significant in the overweight participants (ApoB × weight: P < 0.05). Results showed no association between ApoA1 and CSF biomarkers.

Interpretation: This study is the first to find protective associations of serum ApoB with CSF AD core biomarkers, especially in SCD individuals. It indicated that ApoB may be a potential biomarker for preclinical AD and may play different roles in different stages of AD.

Figure 1

Levels of serum ApoB in different groups. (A) Levels of serum ApoB in a clinical diagnostic construct. CN (N = 288): cognitively normal individuals without subjective and objective cognitive decline; SCD (N = 219): individuals with subjective cognitive decline; (B) Levels of serum ApoB in an ATN biological construct. Stage 0: A‐T‐N‐ (N = 182), Stage 1: A + T‐N‐ (N = 117), Stage 2: A + T+N‐ (N = 8), A + T‐N+ (N = 6), A + T+N+ (N = 38); (C) Levels of serum ApoB in a diagnostic structure combining clinical diagnosis and biomarkers. CN‐ (N = 203): cognitively normal individuals without subjective and objective cognitive decline and with negative CSF Aβ42 [A‐]; CN+ (N = 85): cognitively normal individuals without subjective and objective cognitive decline and with positive CSF Aβ42 [A+]; SCD‐ (N = 135): individuals with subjective cognitive decline and negative CSF Aβ42 [A‐]; SCD+ (N = 84): individuals with subjective cognitive decline and positive CSF Aβ42 [A+]. (D–F) Levels of serum ApoB in A or T or N construct respectively. All intergroup comparisons were tested by Kruskall–Wallis test and Wilcoxon test.

Figure 2

Associations between ApoB and CSF AD biomarkers among participants with different APOEε4 status. (A) Associations of ApoB with CSF Aβ42 in different APOEε4 status. (B) Associations of ApoB with CSF p‐tau in different APOEε4 status. (C) Associations of ApoB with CSF t‐tau in different APOEε4 status. (D) Associations of ApoB with CSF Aβ40 in different APOEε4 status. (E) Associations of ApoB with CSF Aβ42/40 in different APOEε4 status. (F) Associations of ApoB with CSF p‐tau/Aβ42 in different APOEε4 status. (G) Associations of ApoB with CSF t‐tau/Aβ42 in different APOEε4 status. Abbreviations: CSF, cerebrospinal fluid; Aβ, amyloid‐β; p‐tau, phosphorylated tau protein; t‐tau, total tau protein; ApoB, Apolipoprotein B; APOE, apolipoprotein E gene. Multiple linear regression models were used to examine the associations between serum ApoB levels and CSF biomarkers, adjusting for age, sex and education.

Figure 3

Associations between ApoB and CSF AD biomarkers in different diagnostic subgroups. (A) Associations of ApoB with CSF Aβ42 in CN and SCD subgroups. (B) Associations of ApoB with CSF p‐tau in CN and SCD subgroups. (C) Associations of ApoB with CSF t‐tau in CN and SCD subgroups. (D) Associations of ApoB with CSF Aβ40 in CN and SCD subgroups. (E) Associations of ApoB with CSF Aβ42/40 in CN and SCD subgroups. (F) Associations of ApoB with CSF p‐tau/Aβ42 in CN and SCD subgroups. (G) Associations of ApoB with CSF t‐tau/Aβ42 in CN and SCD subgroups. Abbreviations: CN, cognitively normal participants; SCD, participants with subjective cognitive decline; CSF, cerebrospinal fluid; Aβ, amyloid‐β; p‐tau, phosphorylated tau protein; t‐tau, total tau protein; ApoB, Apolipoprotein B. Multiple linear regression models were used to examine the associations between serum ApoB levels and CSF biomarkers, adjusting for age, sex, education, and APOEɛ4 status.

Figure 4

Associations between ApoB and CSF AD biomarkers among different weight participants in SCD subgroup. (A) Associations of ApoB with CSF Aβ42 in normal‐weight and overweight participants. (B) Associations of ApoB with CSF p‐tau in normal‐weight and overweight participants. (C) Associations of ApoB with CSF t‐tau in normal‐weight and overweight participants. (D) Associations of ApoB with CSF Aβ40 in normal‐weight and overweight participants. (E) Associations of ApoB with CSF Aβ42/40 in normal‐weight and overweight participants. (F) Associations of ApoB with CSF p‐tau/Aβ42 in normal‐weight and overweight participants. (G) Associations of ApoB with CSF t‐tau/Aβ42 in normal‐weight and overweight participants. Abbreviations: CSF, cerebrospinal fluid; Aβ, amyloid‐β; p‐tau, phosphorylated tau protein; t‐tau, total tau protein; ApoB, Apolipoprotein B. Multiple linear regression models were used to examine the associations between serum ApoB levels and CSF biomarkers, adjusting for age, sex, education and APOEɛ4 status.