Abstract
Alzheimer disease (AD) is characterized neuropathologically by the presence of senile plaques that are composed of the amyloid-β protein (Aβ). Aβ is an insoluble extracellular deposit consisting of 39-43 amino acids that is cleaved from a larger precursor amyloid-βprecursor protein (β-APP). It has been shown that Aβ proteins extracted from amyloid cores of neuritic plaques contain isomerized and/or racemized Asp residues. Therefore, we hypothesized that a specific secretase (s) may exist in the human brain that can cleave a β-APP peptide bond containing D-Asp at position 1 of the Aβ protein. In the present study, we report data to support the existence of a putative membrane-bound D-β-secretase that can cleave between L-Met-D-Asp at the 1 position of the Aβ with a pH optimum in the neutral pH range. The specific enzyme activity of soluble extracts from AD samples was 22% higher compared to age-matched controls.
Original language | English (US) |
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Pages (from-to) | 125-131 |
Number of pages | 7 |
Journal | Journal of Neuropathology and Experimental Neurology |
Volume | 61 |
Issue number | 2 |
DOIs | |
State | Published - 2002 |
Keywords
- Alzheimer disease
- Enzyme
- High-pressure liquid chromatography (HPLC)
- Protease
- Secretase
ASJC Scopus subject areas
- Pathology and Forensic Medicine
- Neurology
- Clinical Neurology
- Cellular and Molecular Neuroscience