Lens defects and age-related fiber cell degeneration in a mouse model of increased AbetaPP gene dosage in Down syndrome

Topic: Brain proteins, microglia and lab models

Early-onset cataract and Alzheimer's disease occur with high frequency in Down syndrome (trisomy 21), the most common chromosome duplication in human live births. Previously, we used in vivo and lens organ culture models to demonstrate Alzheimer pathophysiology in oxidative stress-related lens degeneration. Currently, well-characterized Alzheimer transgenic mouse models are used to extend these findings. Here, we report on mice carrying a complete copy of a wild-type human AbetaPP (hAbetaPP) gene from the Down syndrome critical region on chromosome 21. hAbetaPP mice produce fiber cell membrane defects similar to those described in human cataracts and increased age-related lens degeneration. hAbetaPP expression and mRNA alternative splicing in human and mouse lens and cornea favor longer, potentially more amyloidogenic forms. Endogenous mouse AbetaPP expression is increased in transgenic lenses, consistent with the cycle of oxidative stress proposed in the mechanism of Alzheimer pathophysiology. Alternative splicing previously designated as neuron-specific occurs in human lens and cornea, and is maintained by hAbetaPP expressed in mouse tissues. These present data implicate AbetaPP in fiber cell formation and in early-onset cataracts in Down syndrome. Finally, our findings provide further support for our hypothesis that Alzheimer pathophysiology contributes to the cataract formation that is increasing in the aging population.

@article{frederikse2002-12466113,
  author  = {Frederikse, P. H. and Ren, X. O.},
  title   = {{Lens defects and age-related fiber cell degeneration in a mouse model of increased AbetaPP gene dosage in Down syndrome}},
  journal = {The American journal of pathology},
  year    = {2002},
  doi     = {10.1016/s0002-9440(10)64475-6},
  pmid    = {12466113},
  url     = {https://doi.org/10.1016/s0002-9440(10)64475-6}
}

Key findings

• Currently, well-characterized Alzheimer transgenic mouse models are used to extend these findings.
• Finally, our findings provide further support for our hypothesis that Alzheimer pathophysiology contributes to the cataract formation that is increasing in the aging population.

Why it matters

Mice carrying a complete copy of the wild-type human amyloid precursor protein gene showed fiber cell membrane defects in the lens and increased age-related lens degeneration. The authors suggest this supports a link between Alzheimer pathophysiology and cataract formation, but this is an animal study and does not test a treatment or cure for Alzheimer's disease.

Study details

• Evidence strengthLow

Read the original

• DOI: 10.1016/s0002-9440(10)64475-6
• PubMed: 12466113
• Original source →
• Free full text: American Journal Of Pathology →

Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).

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Studies this one cites

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• Correlative Memory Deficits, Aβ Elevation, and Amyloid Plaques in Transgenic Mice Science · 1996-10-04 · usefulness score 62/100 · Laboratory science
• A mouse model for Down syndrome exhibits learning and behaviour deficits Nature genetics · 1995-10-01 · usefulness score 54/100 · Down syndrome and Alzheimer's
• Molecular mapping of Alzheimer-type dementia in Down's syndrome Annals of neurology · 1998-03-01 · usefulness score 54/100 · Risk genes beyond APOE
• Expression of APP in brains of transgenic mice containing the entire human APP gene Biochemical and biophysical research communications · 1993-12-01 · usefulness score 37/100 · Down syndrome and Alzheimer's

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