Increased blood BACE1 activity as a potential common pathogenic factor of vascular dementia and late onset Alzheimer's disease

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