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Updated: Jul 18, 2026
15:04
Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils
Published on: September 28, 2019
Beta-amyloid, oxidative stress and down syndrome
Ira T Lott1, Elizabeth Head, Eric Doran
1Department of Pediatrics and Neurology, Alzheimer Disease Research Center, University of California, Irvine, School of Medicine, Irvine, California 92868, USA. itlott@uci.edu
Current Alzheimer Research
|December 16, 2006
Summary
Down syndrome (DS) models Alzheimer disease (AD) by showing progressive amyloid-beta plaque accumulation and neurodegeneration. Early intervention may be possible due to AD-like pathology developing throughout life in DS patients.
Area of Science:
- Neurodegenerative diseases
- Genetics of neurodegeneration
- Alzheimer disease pathogenesis
Background:
- Down syndrome (DS) serves as a valuable model for Alzheimer disease (AD) research.
- Chromosome 21 genes, including APP, SOD-1, Ets-2, and DSCR1, are implicated in neurodegenerative mechanisms relevant to AD.
- Abeta plaque accumulation and neurofibrillary tangles are progressive in DS, mirroring AD pathology.
Purpose of the Study:
- To explore the molecular mechanisms linking Down syndrome to Alzheimer disease pathology.
- To investigate the role of specific genes on chromosome 21 in neurodegeneration.
- To highlight the potential for early intervention in AD through DS research.
Main Methods:
- Analysis of gene expression and protein accumulation related to amyloid precursor protein (APP) processing.
- Assessment of oxidative stress markers, including SOD-1 and glutathione peroxidase activity.
- Examination of age-related somatic DNA mutations and their contribution to neurodegeneration.
Main Results:
- Overexpression of APP in DS leads to abundant Abeta plaques and Braak stage V-VI tangles.
- Intraneuronal Abeta initiates a cascade of oxidative stress and neurodegeneration characteristic of AD.
- Imbalances in SOD-1, Ets-2, and DSCR1 contribute to free radical generation and cell degeneration.
Conclusions:
- Down syndrome recapitulates key Alzheimer disease pathological processes, including Abeta deposition and oxidative stress.
- Gene expression imbalances and somatic DNA mutations exacerbate neurodegeneration in both DS and AD.
- The lifespan progression of AD pathology in DS offers a unique window for early therapeutic strategies.
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