Key result
Factor XI deficiency reduces aortic atherosclerotic lesions ~33% in ApoE knockout mice.
Why the study?
Does factor XI deficiency reduce atherosclerosis and Alzheimer's disease-like pathologies in elderly ApoE knockout mice?
Does factor XI deficiency reduce atherosclerosis and Alzheimer's disease-like pathologies in elderly ApoE knockout mice?
Effect estimate: 33% reduction
Absolute Event Rate: 20% vs 30%
Factor XI deficiency reduces aortic atherosclerosis in elderly ApoE KO mice, but these mice do not develop Alzheimer's disease-like brain pathologies, indicating they are unsuitable models for studying atherosclerosis-related dementia.
Atherosclerosis and Alzheimer's disease (AD) are a major cause of morbidity and mortality in Western societies. These diseases share common risk factors, which are exhibited in old age, including hypertension, diabetes, hypercholesterolemia and apolipoprotein (Apo) ε4 allele. We previously demonstrated that factor XI (FXI) deficiency in mice reduced the atherosclerotic plaque area in coronary sinuses and the aortic arch. This led us to investigate whether FXI deficiency in elderly ApoE knockout (KO) mice would decrease pathological alterations compatible with atherosclerosis and AD. The present study used ApoE/factor XI double KO (ApoE/FXI DKO) mice aged 64 weeks and age‑matched ApoE KO mice to serve as a control group. The ApoE KO mice developed an advanced atherosclerotic lesion area in the aortic arch, which was reduced by 33% in the DKO mice. However, neither atherosclerosis nor AD‑associated pathological alterations in the elderly mice brains were observed in either the DKO mice or the ApoE KO mice. The results advocate a dichotomy between the brain and peripheral blood vessels. Therefore, the ApoE KO and DKO mice cannot serve as mouse models for studying AD or pathological brain changes compatible with atherosclerosis. The mechanism by which ApoE KO protects against brain pathology should be further studied as it may prove helpful for future treatment of senile dementia.
No takes yet. Share an insight, caveat, or question.
Ganor et al. (2017) studied Atherosclerosis and Alzheimer's disease (n=22). Factor XI deficiency vs. ApoE knockout was evaluated on Atherosclerotic lesion area in the aortic arch (33% reduction). Factor XI deficiency in elderly ApoE knockout mice reduced aortic arch atherosclerotic lesion area by 33%, though neither group developed Alzheimer's disease-like brain pathologies.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: