Alzheimer’s disease (AD) affects worldwide ~50 million people. Preclinical research relies mainly on transgenic mouse models overexpressing mutant human proteins that are altered in <5% of AD cases (e.g. β-amyloid and tau), however, despite prominent protein aggregates, they fail to show the dramatic neurodegeneration and cognitive decline of patients, indicating that plaques and tangles may not be the only requirement for AD.
Age is the most determining factor in AD, but is poorly represented in current AD models. This proposal directly aimed at the ageing component in AD, thereby addressing a huge unmet medical need worldwide, which seriously affects QoL, challenges health care systems, and offers unprecedented socio-economical opportunities.
Generating bona fide mouse models for various human DNA repair syndromes we have disclosed a very strong connection between DNA damage, repair and aging including dramatic neurodegeneration. Within the context of ERC-DamAge and ERC-Dementia we discovered striking parallels in neurodegeneration, progressive cognitive decline and genome-wide expression profiles of repair-deficient Ercc1Δ/- mice and human AD. The similarities in expression profiles are an order of magnitude higher than current AD mouse models.
We discovered that nutritional interventions can spectacularly delay neurodegeneration, opening realistic perspectives for combating AD and other neurodegenerative disorders.
Currently, the mouse models are being studied by several pharmaceutical/nutraceutical companies for implementation in their pipeline, enabling development of effective medication for prevention and/or therapy.
