Investigation of amyloid-β peptide production and clearance pathways in different stages of Alzheimer's disease

Alzheimer's disease (AD) is an age-related, progressive decline in cognitive ability. Accumulation and deposition of amyloid-beta (A beta) is still the best-known cause of AD that worsens over time. It is unclear whether the increase in A beta production or the inefficiency of the degradation system causes the accumulation of beta-fibrils during AD development. This research investigated A beta-producing and clearance pathways in different stages of AD. For this purpose, patients were categorized into four experimental groups: patients with mild cognitive impairment, patients with moderate cognitive decline, patients with very severe cognitive decline, and healthy patients as control. Levels of A beta-40, soluble amyloid precursor protein beta (sAPP beta), (ACE), and insulin-degrading enzyme (IDE) were determined by ELISA kits and immunoblotting in serum samples. According to the results, the levels of A beta-40 and sAPP beta increased in AD patients from an early stage, and levels were maintained in progressive AD stages. MMP-9 also increased in the early stage, but its content decreased with disease development. MMP-3 was significantly higher in the three stages of AD compared to the control patients. However, IDE, NEP, and ACE enzymes as clearing systems decreased in all studied AD samples, with their reductions more remarkable in the middle and late stages. The results showed that multiple A beta-degrading enzymes such as NEP and IDE in AD patients decline as AD progresses, while A beta-40 and sAPP(beta increased from the early stage of the disease. Therefore, it could be concluded that detection of the dementia phase is a critical step for therapeutic strategies.