G.Petzold, M.Nedergaard, M.Heneka, C.Göritz, S.Oliet
DACAPO-AD: Deciphering Interactions of Acquired Risk Factors and ApoE-mediated Pathways in Alzheimers Disease
Alzheimer's disease & other dementias
Alzheimers disease (AD) imposes an enormous personal burden on patients and caregivers, as well as a tremendous socio-economic impact on society. However, there is a paucity of pharmaceutical or interventional strategies that have a proven impact on the incidence or progression of AD. One reason is that most models are based on familial (early-onset) AD pathogenesis, but typically do not reflect the multifactorial pathophysiology of sporadic (late-onset) AD, which is associated with genetic risk factors such as the apolipoprotein E (ApoE) ?4 polymorphism, as well as environmental risk factors, such as a high-fat diet, cardiovascular disease, traumatic brain inju- ry, systemic inflammation and perturbed sleep regulation. We aim to create novel AD models that combine the most common genetic risk factor (ApoE-?4) and many of the most prevalent acquired risk factors, enabling us to better understand the multi- factorial and highly prevalent, yet currently understudied, interplay between inherited and acquired risk factors in the pathophysiology of late-onset AD. These models may therefore be more predictive of possible translatability into clinical studies, and may potentially lead to the develop- ment of new avenues of primary prevention or treatment.