Abstract
Late onset Alzheimer disease (LOAD) is traditionally considered as a separate disease from vascular dementia (VAD). However, growing evidence suggests that β-amyloid (Aβ) accumulation, that initiates LOAD-related neurodegeneration, is preceded by vascular events. Previous in vitro studies showed that β-secretase 1 (BACE1), the key-enzyme of amyloidogenesis, is upregulated by cerebrovascular insult; moreover, its activity is increased both in brain and serum of LOAD patients. We aimed to investigate whether BACE1 serum activity is altered also in dementias related, or not, to cerebrovascular disease. Thus, we evaluated serum BACE1 activity in a sample of individuals, including patients with LOAD (n. 175), VAD (n. 40), MIXED (LOAD/VAD) dementia (n. 123), other types of dementia (n. 56), and healthy Controls (n. 204). We found that BACE1 was significantly higher not only in LOAD (+ 30%), but also in VAD (+ 35%) and MIXED dementia (+ 22%) (p < 0.001 for all), but not in the other types of dementia (+ 10%). Diagnostic accuracy was 77% for LOAD, 83% for VAD, and 77% for MIXED dementia. In conclusion, we showed for the first time that the increase in peripheral BACE1 activity is a common feature of LOAD and VAD, thus underlying a further pathogenic link between these two forms of dementia.
Highlights
Late onset Alzheimer disease (LOAD) is traditionally considered as a separate disease from vascular dementia (VAD)
Based on this corollary of evidences, in the present study we investigated whether an increase in serum BACE1 activity is a specific feature of LOAD or might characterize VAD
Years of formal education, as well as Mini Mental State Examination (MMSE), instrumental activity of daily living (IADL) and basic activities of daily living (BADL) score were higher in Controls compared with all dementia groups
Summary
Late onset Alzheimer disease (LOAD) is traditionally considered as a separate disease from vascular dementia (VAD). Increase in Aβ burden caused by vascular factors could occur through the impairment of the clearance (vascular pathway is estimated to be a major route of removal of Aβ from the b rain12) and/or in the production of the p eptide11 Relevant to this context, in vivo and in vitro studies showed that hypoperfusion/hypoxia, and induced oxidative stress, may facilitate Aβ production by activating the APP cleavage enzyme β-secretase 1 (BACE1). We found that LOAD patients has significantly higher levels of serum BACE1 activity compared to controls, and this difference is independent of possible confounders including age, gender, and other risk factors for d ementia17 Based on this corollary of evidences, in the present study we investigated whether an increase in serum BACE1 activity is a specific feature of LOAD or might characterize VAD. We evaluated the serum levels of BACE1 in a large sample of elderly individuals (n. 598) including patients affected by LOAD, VAD, mixed LOAD-VAD dementia (MIXED), and other type of dementia, in comparison with cognitively healthy subjects
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