Aging-US: Early elevation of BACE1 in dementia
12-20-2021Aging-US published "Early elevation of BACE1 in dementia" which reported that interest in the role of Beta-secretase1 in Alzheimer’s disease pathogenesis and patho- physiology has been remarkably growing in the last 10 years.
This transmembrane aspartyl protease catalyzes the rate-limiting step of the sequential cleavage of amyloid precursor protein to form Aβ fragments which will then aggregate in so-called senile plaques.
Dr. Carlo Cervellati from The University of Ferrara said, "The burst of published literature on the topic mainly stems from the potential significance of this key- enzyme of amyloidogenic pathway as pharmacological target."
The burst of published literature on the topic mainly stems from the potential significance of this key- enzyme of amyloidogenic pathway as pharmacological target.
Based on our published research we have suggested another possible clinical application of BACE1. Indeed, inspired by mounting evidence of BACE1 increase in brain, CSF, and plasma, in AD patients compared to healthy controls, we have started to evaluate the diagnostic performance of serum activity of the enzyme.
Taking a stock of our results, from the analysis of total 817 subjects, we have found that serum BACE1 activity is around 30% higher in patients with AD, vascular dementia, mixed dementia compared to controls.
This recent investigation has revealed that serum BACE1 activity:
1) Is similarly higher in both aMCI and naMCIs as compared to healthy controls;
2) Is higher in aMCI converting to dementia compared to stable MCI when considering patients with a less compromised cognitive status;
3) Is not a predictor of conversion from aMCI to dementia.
The Cervellati Research Team concluded in their Aging-US Research Output, "BACE1 up-regulation might be one of the first abnormal event in AD (and VD). Within this long preclinical phase of the disease, which lasts years before the diagnosis of MCI state, BACE1 may be the key- player of the initial, and still asymptomatic, neuropathological changes. In this time frame, the evaluation of its serum activity might have clinical relevance as early biomarker, mostly for screening subjects to enroll in clinical trials. The time when Aβ accumulation is the prominent alteration, and the specific weight of other pathogenic actors is still relatively low, BACE1 could also be candidate therapeutical target. As recently suggested by Panza et al.[2], large random clinical trials with BACE1 inhibitors have failed (for lack of benefit or the occurrence of adverse effects) most likely because they were administered on patients experiencing the irreversible phase of the disease (mild-to-moderate AD). Indeed, in these treated patients the significant decrease in cerebrospinal fluid Aβ (but not in amyloid- PET), is not accompanied by cognitive benefit [2]. This could mean that BACE1-mediated formation of Aβ has lost its “primacy”, and other pathogenic players could have taken over the lead."
Full Text - https://www.aging-us.com/article/203727/pdf
Correspondence to: Carlo Cervellati email: crvcrl@unife.it
Keywords: Alzheimer’s disease, amyloid- β, BACE1, mild cognitive impairment
About Aging-US:
The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population.
The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.)
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