The liver and systemic processes in Alzheimer´s disease

Alzheimer´s disease (AD) is the most common neurodegenerative disease leading to dementia. The disorder is fatal and lacks established prevention strategies and cure.

Approximately 20% of the Scandinavian population carriers the APOE4 gene variant, which increases the risk of AD by 5-15 fold. Interestingly, the APOE4-promoted risk of disease appears to vary between populations and may also be modifiable.

We have previously demonstrated that plasma apolipoprotein E (apoE) levels, derived from the liver, are altered in APOE4-carriers and associated with AD biomarker levels and cognition, specifically in Europeans.

We have also demonstrated that an APOE4 genotype of the liver contributes to pathological alterations in the brain and a recent study in support of our findings proposed that effects on the blood-brain-barrier may contribute to this outcome.

In the current study we aim to further investigate how manipulation of plasma liver-derived apoE levels in vivo influences key processes in the brain. We also aim to in detail study the liver amyloid-beta degrading capacity and whether it varies with APOE genotype.

Clearance of amyloid-beta across the blood-brain-barrier for degradation by the liver is key to control brain amyloid-beta pathology and can be increased by recently approved amyloid-beta directed therapy.

The results from our project will provide crucial new insights into the yet underexplored role of the liver and its processes in the pathophysiology of AD.