Apolipoprotein E and matrix remodeling – a link to neurodegeneration in Alzheimer’s disease

Abstract

Apolipoprotein E (APOE) is a glycoprotein primarily produced by astrocytes and microglia. It plays a crucial role in complexing with amyloid β (Aβ) to accelerate its clearance. APOE genotyping holds great importance in determining whether an individual carries the APOE ε2/ε3/ε4 allele and the corresponding APOE2/E3/E4 protein isoform. Carrying the APOE ε4 allele has been associated with an increased risk of Aβ accumulation, amyloid plaque formation, and late-onset Alzheimer's disease (LOAD). The identification of novel biomarkers that indicate the earliest pathophysiological processes involved in Alzheimer's disease (AD) and the analysis of their diagnostic value in patients, especially through less invasive and cost-effective procedures that can visualize AD in a minimally invasive manner, are the focuses of numerous researchers. Matrix metalloproteinases (MMPs), their tissue inhibitors (TIMPs), and activators play a significant role in extracellular matrix remodeling, disruption of blood-brain barrier integrity, prolonged neuroinflammation, and Aβ clearance. These biomarkers are showing promise as potential blood-based diagnostic markers for patients with AD. In this context, we will discuss the possible mechanisms underlying the interrelation between APOE ε4 carrier status, matrix remodeling enzymes, and neurodegeneration in AD. Additionally, we will explore the diagnostic accuracy of these biomarkers in AD dementia patients based on the results obtained by our research group.