Elevated Cerebrospinal Fluid BACE1 Activity in Incipient Alzheimer Disease

Abstract

Background: We used a sensitive and specific ␤-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1) assay to determine the relationship between BACE1 activity in cerebrospinal fluid (CSF) and markers of APP metabolism and axonal degeneration in early and late stages of Alzheimer disease (AD).

Amyloid β and APP as biomarkers for Alzheimer’s disease

“…Levels of sAPP-α and sAPP-β are unaltered (Olsson et al, 2003;Zetterberg et al, 2008), or mildly elevated (Lewczuk et al, 2008) in sporadic AD, and correlate tightly with each other (Lewczuk et al, 2008;Zetterberg et al, 2008). Although BACE1 is a membrane-bound protein, an extracellular isoform produced by membrane-shedding is found in CSF, and CSF BACE1 activity is increased in AD patients (Holsinger et al, 2006;Holsinger et al, 2004;Verheijen et al, 2006), as well as in subjects with mild cognitive impairment (MCI) and prodromal AD, as compared to controls Zhong et al, 2007).…”

New Frontiers in Alzheimer's Disease Diagnosis

“…Several independent observations indicate the presence of higher BACE1 levels and activity in the CSF of MCI and AD samples when compared to controls [97][98][99][100]. BACE1 activity is also increased in CJD samples [101] suggesting common pathological mechanisms among both diseases.…”

Brain Lipids in the Pathophysiology and Treatment of Alzheimer’s Disease

“…Mutations in the BACE-1 gene have not been related to AD but elevated levels of this enzyme have consistently been found in both the brain and CSF of patients with AD [101][102][103]. Since β-secretase activity is pathologically elevated in AD, BACE1 inhibition has been addressed as a potential therapeutic approach to combat AD.…”