The relationship between amyloid-β peptide spectrum and the spastic paraparesis phenotype in autosomal dominant Alzheimer's disease.

ABSTRACT:

Background

More than 300 mutations in presenilin 1 (PSEN1) lead to autosomal dominant Alzheimer's disease (ADAD). PSEN1, as the catalytic subunit of γ-secretase, generates amyloid-β (Aβ) peptides through a sequential proteolysis of the amyloid precursor protein (APP). While ADAD typically presents with progressive cognitive decline, ~ 25% of PSEN1 mutation carriers develop spastic paraparesis (SP), a debilitating motor condition. The molecular basis of this phenotypic heterogeneity remains unknown. This study examines Aβ profiles generated by PSEN1 variants associated with different clinical presentations with the aim of exploring potential associations between different Aβ profiles and clinical heterogeneity.

Methods

We analysed reported Aβ peptide profiles generated in vit

SUBMITTER: Zoltowska KM 

PROVIDER: S-EPMC12659523 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature