Year: 2008
Type: article
Study design: Observational Study
Abstract: The pathogenesis of Alzheimer disease (AD) involves increased amyloidogenic processing of amyloid precursor protein (APP) in the brain. Here, we test the hypothesis that elevated cerebrospinal fluid (CSF) β-site APP-cleaving enzyme 1 (BACE1) activity may reflect this process. CSF BACE1 activity was evaluated in relation to CSF levels of secreted APP and amyloid-β (Aβ) isoforms and the axonal degeneration marker tau in 87 subjects with probable AD, 32 non-demented controls and 113 patients with mild cognitive impairment (MCI), who were followed for 3–6 years. AD patients had higher CSF BACE1 activity (median [range] 30 [11–96] pM) than controls (23 [8.3–43] pM, P = .022). MCI patients who progressed to AD during follow-up had higher baseline BACE1 activity (35 [18–71] pM) than MCI patients who remained stable (29 [14–83] pM, P < .001) and MCI patients who developed other forms of dementia (20 [9.8–56] pM, P = .001). BACE1 activity correlated positively with CSF levels of secreted APP isoforms and Aβ40 in the AD and control groups and in all MCI subgroups (P < .05), except for the MCI group that developed AD. In contrast, there was no correlation between BACE1 and Aβ42 in any of the groups. Positive correlations were found between CSF BACE1 activity and tau levels in all groups (r ≥ 0.6, P ≤ .009). Elevated BACE1 activity may contribute to the amyloidogenic process in sporadic AD and is associated with the intensity of axonal degeneration.
Source: Alzheimer s & Dementia
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2162299434