Age-related behavioral and molecular landmarks in new mouse models for studying Alzheimer's disease in Down syndrome - PubMed
3 hours ago
- #Alzheimer's disease
- #Down syndrome
- #mouse models
- Down syndrome (DS) is a major genetic cause of intellectual disability and Alzheimer's disease (AD), with over 90% developing DSAD.
- Triplication of the APP gene on chromosome 21 drives early Aβ accumulation, but other genes also contribute to pathology.
- Two new DSAD mouse models with partial humanization of Aβ were developed to address limitations of current models.
- These models exhibit early AD features: cognitive deficits, hyperactivity, tau hyperphosphorylation, and endolysosomal dysfunction.
- APP processing shifts toward β-secretase, increasing CTF-β and altering Aβ dynamics.
- Aβ humanization modulates behavior, improving some cognitive tasks but enhancing anxiety traits.
- Models show myelinosome formation and impaired autophagic flux, aligning with human AD pathology.
- They serve as tools to study early DSAD mechanisms and therapies, pending a fully humanized trisomic model.