Enzymatic Biomarkers for Early Diagnosis of Alzheimer's Disease:Uncovering Key Targets and Mechanisms

Alzheimer's Disease (AD) is a neuronal illness that disrupts behavior, cognitive, and functional abilities. The development of AD is progressive, continuous, and irreversible, from preclinical illness to mild cognitive or even behavioral disturbance to dementia (a medical brain condition) triggered by AD. Worldwide accepted hypotheses of AD are called the amyloid-cascade and hyperphosphorylated tau-cascade hypotheses, and enzymes are implicated in the pathophysiology of AD directly or indirectly. There is an implication of enzymes in the pathophysiology of AD. Enzymes include proteases (e.g., neprilysin), kinases (e.g., glycogen synthase kinase-3), cholinergic enzymes (e.g., acetylcholinesterase), metalloproteinases (e.g., matrix metalloproteinases), and oxidative stress-related enzymes (e.g., superoxide dismutase). However, during abnormal or early Alzheimer's Disease (AD) conditions, the activity and expression of these enzymes are altered in biological samples such as blood, urine, and cerebrospinal fluid (CSF) in patients with early AD when examined. These alterations in enzyme activity in early AD demonstrate the potential of these enzymes as biomarkers. Early detection of AD in its early stages is crucial for effective control and treatment of the disease. Existing diagnostic techniques rely mainly on neuroimaging and medical evaluation. Through this technique, we can only diagnose the advanced or late stage of AD. Therefore, there is a crucial need to establish valid biomarkers that might assist in the early detection of AD. Enzymatic targets have come to light as a promising alternative for the development of selective and sensitive diagnostic assays. This review aims to investigate the potential of enzymes as an enzymatic target for early AD diagnosis, emphasizing their diagnostic use and fundamental mechanisms. Here, we summarize the role or implication of 25 enzymes in the pathophysiology of AD in the early stage.