CRISPR-Cas9: A Promising Tool in Developing Alzheimer’s Disease Treatment

Abstract

Alzheimer’s disease (AD) impacts millions of people worldwide, causing cognitive impairment that can get more and more severe as the patients age. Such a disease can also severely impact patients’ lives in the late stage. AD is a sporadic and familial disease. Beta-amyloid (Aβ) and hyperphosphorylated tau protein aggregates directly link to AD pathogenesis, leading to synaptic dysfunction and cognitive decline. When amyloid beta precursor protein (APP) has mutations on the genetic level, patients are likely to have familial AD. In addition, the presenilin (PSEN) gene is another target gene for AD research. Unfortunately, the existing therapies are still ineffective as they can only delay AD progression but cannot stop nor reverse it. Recently, CRISPR-Cas9 has emerged as a promising gene-editing tool in AD research. CRISPR-Cas9 is an outstanding tool compared with the first two generations of gene editing techniques, as CRISPR-Cas9 is cheaper and more efficient. It can create desired mutations in precise positions to target gene sequences, thus potentially manipulating the genes related to familial AD. By mitigating the overproduction of Aβ and tau protein aggregates, researchers aim to slow down or halt the disease progression. CRISPR-Cas9 has significant potential in constructing AD models, screening AD pathogenic genes, and developing targeted therapies for AD. Such a technique offers scientists a better understanding of AD pathogenesis and enlightens more efficient genetic therapies. This review systematically illustrates the CRISPR-Cas9 system and further explains its implementation in AD model constructions, pathogenic genes searching, and potential treatment for AD.