Risk factors for neuropathological hallmark lesions and cell death in preclinical and symptomatic Alzheimer's disease: a chance for age-of-onset prediction?

Alzheimer's disease (AD) is a neurodegenerative disorder, which is characterized by specific pathological hallmark lesions. These lesions develop first in a limited area of the brain and then expand into further brain regions until nearly the entire brain is involved in these pathologies. The first lesions are usually seen in cognitively normal individuals and are considered to represent a preclinical stage of AD. Such stepwise expansion patterns of AD lesions allow to determine the stage of the disease of a patient. Because treatment of symptomatic patients has not yet been successful, one strategy currently used is testing preventive treatments that may stop disease progression. In familial AD, single gene mutations cause the disease and can identify individuals at risk. In sporadic AD, such a direct genetic link is not given. However, a "polygenic hazard score" has been established to describe the genetic risk for AD. In this project, we want to make use of risk genes for sporadic AD to determine their effects on the expansion of the pathological hallmark lesions of AD, including different types of neuronal cell death, and to use these data to predict the individual age-of-onset of distinct AD lesions. Prediction of the age-of-onset of preclinical AD lesions will help to detect individuals that are potential candidates for AD prevention trials.

Keywords:GENETIC EPIDEMIOLOGY, ALZHEIMER'S DISEASE, GENETICS, NEUROPATHOLOGY

Disciplines:Molecular diagnostics, Morphological sciences not elsewhere classified, Neurological and neuromuscular diseases

Project type:Collaboration project