Our results suggest that the mitochondrial DNA background plays an important role in modifying the disease phenotype but nuclear modifiers, epigenetic and environmental factors may also influence the severity of disease.
However, the mere presence or absence of an established, modifiable risk factor (for example, smoking, diabetes), should not override or modify the disease grade assigned based on the percentage of bone loss/age ratio, which comprehensively reflects a patient's past susceptibility.
Most efforts to modify the disease mechanism so far have tried to counter the buildup in the brain of beta-amyloid, a protein that forms sticky plaques.
"The drugs available at the moment can hold cognitive function, but they don't modify the disease," says neurologist Professor Giovanna Mallucci, programme leader at the Medical Research Council's toxicology unit.
Reporting in the Aug. 20 issue of Nature Genetics, the researchers provide evidence for modified penetrance, in which genetic variants that regulate gene activity modify the disease risk caused by protein-coding gene variants.
Despite the years of research that have provided valuable insights into the pathology of AD, challenges remain in (1) developing and testing therapies that modify the disease course of AD and (2) guiding patients effectively through an optimized diagnostic and healthcare journey.
A mechanistic approach to the discovery of key pathogenic brain modifications causing seizure onset, recurrence and progression is instrumental for designing novel and rationale therapeutic interventions that could modify the disease course or prevent its development.
Imaging of tau lesions in living tauopathy patients has been enabled recently, and in vivo quantification of tau pathologies would improve accuracy of diagnosing these disorders and facilitate objective assessments of anti-tau treatments capable of modifying the disease process.
For this purpose, chemical agents are screened for their ability to interact with the target, and agents that can interact with the target have the potential of modifying the disease process.
