Navigation Links
Enzyme BACE1 may be important in predicting onset of Alzheimer disease
Date:12/11/2013

Philadelphia, PA, December 12, 2013 The critical enzyme beta-secretase1 (BACE1) is known to be elevated in brains with sporadic Alzheimer disease (AD). Scientists have now found increased levels of BACE1 in brains with mild cognitive impairment (MCI), suggesting that BACE1 activity is important for conversion of mild cognitive impairment to AD and may be an early indicator of AD. The results are published in the January issue of The American Journal of Pathology.

Understanding the early events of AD is key to effective diagnosis and treatment. Two of the major pathological characteristics of AD are neuritic plaques and neurofibrillary tangles, which are used to diagnose or confirm AD at autopsy. Neuritic plaques, which are also known as senile, dendritic, or amyloid plaques, consist of deteriorating neuronal material surrounding deposits of a sticky protein called amyloid beta peptide (Aβ). Neurofibrillary tangles consist of highly phosphorylated forms of the microtubule-associated protein tau.

Following on earlier discoveries that BACE1 activity and protein expression are significantly increased in AD brains, researchers have now found raised levels of BACE1 enzymatic activity in brain tissue from patients with MCI, a precursor to AD. BACE1, also known as β-site amyloid precursor protein cleaving enzyme, is an aspartic protease and is a critical enzyme that promotes Aβ generation.

In the current study, researchers examined autopsied brain tissue from 18 patients with clinically well-characterized AD, 18 patients with MCI, and 18 non-demented patients. They found that BACE1 enzymatic activity was significantly increased in both MCI and AD brains. In 11 of 18 MCI patients, who had undergone a mini-mental state examination (MMSE) before death, the brain cortex BACE1 levels increased during early dementia followed by a precipitous decrease as the decline in cognition progressed. Increased BACE1 activity correlated with plaque numbers and cognition status. Interestingly, they also observed that there was no significant difference in BACE1 activity between MCI and AD.

The researchers also found an increase in tumor necrosis factor alpha (TNFα) in MCI brains. TNFα is an inflammatory cytokine or cell signaling protein required for amyloid protein induced neuronal death. Biochemical examination of the autopsy tissue showed that TNFα rather than other cytokines increases the response to BACE1 protein expression. The increased levels of TNFα in MCI and AD patients were not significantly different from each other.

"There is more and more evidence that BACE1 is intricately involved in the development of AD," says the study's lead investigator Yong Shen, PhD, of the Center for Advanced Therapeutic Strategies for Brain Disorders at Roskamp Institute, Sarasota, Florida. "Our previous studies have demonstrated elevated BACE1 enzymatic activity in AD brains and in the cerebrospinal fluid from MCI and AD patients. Our findings here suggest that BACE1 increases early in the course of MCI and is possibly induced by inflammatory molecules like TNFα and that BACE1 enzymatic activity may be important for conversion of MCI to AD. Importantly, we found that the BACE1 activity in tissue from people with MCI was significantly increased by 27%, compared with that from people with no dementia.

"We believe that BACE1 activity precedes the clinical diagnosis of AD and could be an early indicator of neuronal dysfunction or pathology in AD. Moreover, it may be a good therapeutic target for AD, as evidenced by recent promising clinical trials on BACE1 inhibitors," he concludes.


'/>"/>

Contact: Eileen Leahy
ajpmedia@elsevier.com
732-238-3628
Elsevier Health Sciences
Source:Eurekalert

Related biology news :

1. Spanish scientists identify a new ancestral enzyme that facilitates DNA repair
2. Crafting a better enzyme cocktail to turn plants into fuel faster
3. Wistar scientists decipher structure of NatA, an enzyme complex that modifies most human proteins
4. RI Hospital: Absence of specific enzyme in cartilage can lead to benign tumors in mice
5. Fear factor: Missing brain enzyme leads to abnormal levels of fear in mice, reveals new research
6. Antiviral enzyme contributes to several forms of cancer, University of Minnesota researchers say
7. Novel enzyme from tiny gribble could prove a boon for biofuels research
8. Combining strategies speeds the work of enzymes
9. Protein improves efficacy of tumor-killing enzyme
10. Enzymes allow DNA to swap information with exotic molecules
11. DNA catalysts do the work of protein enzymes
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/9/2016)... 9, 2016 Elevay is currently ... expanding freedom for high net worth professionals seeking travel ... globally connected world, there is still no substitute for ... duplicate sealing your deal with a firm handshake. This ... taking advantage of citizenship via investment programs like those ...
(Date:4/26/2016)... and LONDON , April ... part of EdgeVerve Systems, a product subsidiary of ... today announced a partnership to integrate the Onegini ...      (Logo: http://photos.prnewswire.com/prnh/20151104/283829LOGO ) ... their customers enhanced security to access and transact ...
(Date:4/15/2016)... Research and Markets has announced ... 2016-2020,"  report to their offering.  , ... global gait biometrics market is expected to grow ... 2016-2020. Gait analysis generates multiple variables ... to compute factors that are not or cannot ...
Breaking Biology News(10 mins):
(Date:5/20/2016)... CA (PRWEB) , ... May 20, 2016 , ... The ... 10 of its most experienced veterinary clients have treated over 100 of their own ... edge technology to provide the highest level of care for their patients. , ...
(Date:5/19/2016)... MAPLE RIDGE, British Columbia , May 19, ... of AdvanTec Global Innovations Inc. (AGI), based out ... recently added Greenlane Biogas Ltd. to its ... a 2-year contract manufacturing agreement. AFS along with ... Bending Technologies (ABT) is a vertically integrated industrial ...
(Date:5/18/2016)... Irvine, Calif. (PRWEB) , ... May 18, 2016 , ... ... had awarded the Luis Villalobos Award to Cognition Therapeutics at the annual ACA Summit ... innovative company that is financed by one of ACA’s member angel groups. It is ...
(Date:5/18/2016)... ... May 18, 2016 , ... The Academy of Model Aeronautics has ... dream of reaching a total of $1 million in awarded scholarships. , The AMA ... school graduates from across the nation has helped bring the total of AMA scholarships ...
Breaking Biology Technology: