BACE1 Levels by APOE Genotype in Non-Demented and Alzheimer’s Post-Mortem Brains

Boris      Decourt; Amanda      Gonzales; Thomas      G. Beach; Michael      Malek-Ahmadi; Aaron      Walker; Lucia      Sue; Douglas      G. Walker; Marwan      N. Sabbagh

Abstract

The APOE genotype is a known susceptibility factor for Alzheimer’s disease (AD). It is apparent that the presence of the APOE ε40 allele increases the risk for developing AD, lowers the age of onset in AD, and may influence the pathological burden seen in AD. In this study, we asked whether BACE1 levels differ by APOE genotype in the AD and non-demented (ND) brain. We isolated mid-frontal cortex (MFC) and mid-temporal cortex (MTC) from post-mortem ND and AD subjects that were APOE ε3/3, ε3/4, ε4/4 carriers. All AD subjects met NINDS-ADRDA and NIA-Reagan criteria for a diagnosis of AD. The MFC and MTC were homogenized and the lysates underwent ELISA and Western blotting for BACE1. The ELISA revealed that total BACE1 levels were lower in the MFC of AD compared to ND subjects. Furthermore, in APOE ε4 carriers BACE1 levels were lower than ε3/3 carriers in the ND frontal cortex. No difference in BACE1 levels was observed in AD MFC and in ND and AD MTC tissues. The ELISA results were confirmed by Western blotting. Our data suggest that brain BACEl levels may be influenced by the apolipoprotein E genotype before the onset of AD, providing an alternative explanation for the lower amyloid beta 42 levels in CSF in ND and AD subjects.

Keywords: Alzheimer’s disease, APOE, BACE1, brain, ELISA, frontal cortex

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