Amyloid-beta precursor protein (Swedish mutation) genomic DNA (APPswe)

The APPswe mutant allele genomic DNA refers to a specific pathogenic variant of the Amyloid Precursor Protein (APP) gene, characterized by a double mutation (K670N and M671L) at the N-terminus of the amyloid-beta (Aβ) sequence (Mullan et al., 1992, Nature Genetics). This mutation, first identified in Swedish families, significantly increases the proteolytic cleavage of APP by beta-secretase (BACE1), leading to an overproduction of neurotoxic Aβ peptides (Haass et al., 1995, Nature Medicine). This process is a primary driver in the pathogenesis of early-onset familial Alzheimer's disease (EOFAD). As a therapeutic target, the genomic DNA is primarily addressed through gene-editing technologies like CRISPR/Cas9, which aim to selectively disrupt or correct the mutant allele while sparing the wild-type allele (Gyorgy et al., 2019, Molecular Therapy). Therapeutic strategies focusing on this target seek to reduce the total burden of amyloid plaque formation in the brain. Challenges include ensuring high specificity to avoid silencing the healthy APP allele, which has essential physiological roles in synaptic plasticity and neuronal health. Additionally, the delivery of gene-editing components across the blood-brain barrier remains a significant hurdle for clinical application.

Other names

APP Swedish mutationKM670/671NL mutationSwedish APP mutant alleleAPP-SweAmyloid beta precursor protein Swedish mutant

Allele-specific gene disruption or correction via genome editing