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
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Elsevier Health Sciences