Therefore, revealing the underlying mechanism of BACE1 in the pathogenesis of AD might have a significant impact on the future development of therapeutic agents targeting dementia.
The evidence that a pathogenic APP mutation causes an early enhancement of BAD-Glu suggests that alterations of BACE1 processing of APP in glutamatergic synaptic vesicles could contribute to dementia.
Few of them, i.e., platelet tau, AβPP (particularly with regards to coated platelets) and secreted ADAM10 and BACE1 show the most promise to be taken forward into clinical setting to diagnose dementia.
BACE1 activity and sAβPPβ concentration were measured in patients with AD dementia (n = 56) and mild cognitive impairment (MCI) due to AD (n = 76) with abnormal routine AD CSF markers, in patients with MCI with normal CSF markers (n = 39), and in controls without preclinical AD (n = 48).
Subjects with MCI who converted to probable AD dementia at follow-up examinations exhibited significantly higher BACE1 activity compared with cognitively stable MCI nonconverters and showed higher levels of BACE1 activity than patients with AD.
Knockdown of endogenous miR-9 via lentiviral vector-mediated delivery of its antisense molecule (lenti-pre-AMO-miR-9) reduced the vulnerability to dementia, reversed the increase in BACE1 expression, and ameliorated the reduction in CREB expression triggered by 2VO.
Our work provides a new insight that BACE1 overexpression not only promotes neuritic plaque formation but may also potentiate neurodegeneration mediated by SET elevation in Alzheimer-associated dementia in DS.
We conclude that miR-195 may play a key role in determining dementia susceptibility in 2VO rats by regulating APP and BACE1 expression at the post-transcriptional level, and exogenous complement of miR-195 may be a potentially valuable anti-dementia approach.
Ischemic cerebrovascular diseases, usually involved in hypoxia and reoxygenation, have been reported to increase the risk of dementia such as Alzheimer's disease (AD). beta-site amyloid protein precursor (APP)-cleaving enzymes (BACE1) have been identified to participate in the secretion of beta-amyloid peptides (Abeta), and its expressive alteration would contribute to the AD neuropathology.