Bilateral Hippocampal Volume Mediated the Relationship Between Plasma BACE1 Concentration and Memory Function in the Early Stage of Alzheimer’s Disease: A Cross-Sectional Study
Affiliations: [a]
Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China
| [b]
Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China
Correspondence:
[*]
Correspondence to: Zhongwu Sun MD, PhD, Professor of Neurology, Department of Neurology, the First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei, Anhui Province 230022, China. Tel.: +86 10 62922328; E-mail: sunzhwu@126.com.
Note: [1] These authors contributed equally to this work.
Abstract: Background:β-site amyloid precursor protein cleaving enzyme 1 (BACE1) is a key enzyme in the formation of amyloid-β (Aβ) protein. Increasing evidence suggests that BACE1 concentration is a potential biomarker for Alzheimer’s disease (AD). Objective:To evaluate the correlations between plasma BACE1 concentration, cognition, and hippocampal volume at different stages of the AD continuum. Methods:Plasma BACE1 concentrations were measured in 32 patients with probable dementia due to AD (ADD), 48 patients with mild cognitive impairment (MCI) due to AD, and 40 cognitively unimpaired (CU) individuals. Memory function was evaluated using the auditory verbal learning test (AVLT), and voxel-based morphometry was used to analyze bilateral hippocampal volumes. Correlation and mediation analyses were performed to investigate the associations between plasma BACE1 concentration, cognition, and hippocampal atrophy. Results:The MCI and ADD groups exhibited elevated BACE1 concentrations compared with the CU group after adjusting for age, sex, and apolipoprotein E (APOE) genotype. Increased BACE1 concentration was found in AD continuum patients who were APOE ɛ4 carriers (p < 0.05). BACE1 concentration was negatively associated with the scores of the subitems of the AVLT and hippocampal volume (p < 0.05, false discovery rate correction) in the MCI group. Moreover, bilateral hippocampal volume mediated the relationship between BACE1 concentration and recognition in the MCI group. Conclusion:BACE1 expression increased in the AD continuum, and bilateral hippocampal volume mediated the effect of BACE1 concentration on memory function in patients with MCI. Research has indicated that the plasma BACE1 concentration might be a biomarker at the early stage of AD.
