In silico modeling of pathogenic or possibly pathogenic point mutations in PSEN2

Abstract

Alzheimer's disease (AD) is the most common form of neurodegenerative disorder that affects memory, thinking, and behavior. 3 genes found to be involved in early-onset AD encode amyloid precursor protein (APP), presenilin1 (PSEN1), and presenilin2 (PSEN2). Presenilin mutations play a key role, with more than 200 mutations described for PSEN1 and approximately 40 for PSEN2. However, whether mutations cause disease or have effects on protein function is often unknown. For further study, such as genetic counseling and pathogenesis, the important thing we need do is to classify mutations into "pathogenic" or "not pathogenic". Building a structural context in cell for all mutations is expensive and time consuming. In this study, we summarized substitution mutations in the PSEN2 gene and attempted to identify pathogenic mutations using Polyphen2 (polymorphism phenotyping v2), SIFT (Sorting Intolerant From Tolerant), and 3-D structure analysis techniques.