Approved Research

A UK Biobank longitudinal study of clonal haematopoiesis and risk of Alzheimer's Disease

Lay summary

Considering the causes of Alzheimer's disease, hereditary factors come to the fore for Early Onset Alzheimer's Disease. However, the causes of Late-Onset Alzheimer's Disease, which constitutes the majority of the patient population, have not been clarified yet. Age is the most prominent risk factor for Alzheimer's Disease, but the effects of ageing on the disease are not fully understood. With ageing, mutations which are not acquired congenitally occur in blood cells. These mutations have been found to be less than 1% in people with age >40, about 10% in people with age >70, and about 15-20% in people with age >90 in investigations involving people without haematological malignancy. This condition has been termed clonal haematopoiesis of indeterminate potential. Individuals with these mutations are at risk of developing haematological malignancies such as Myelodysplastic Syndrome, Acute Myeloid Leukaemia, and Lymphoma. In addition, these mutations increase the risk of coronary heart disease, myocardial infarction and mortality. It has been discovered that these mutations, the prevalence of which increases with ageing, lead to some gene activations and inflammatory effects. We intend to use Whole Exome Sequencing data from the UK Biobank to investigate whether clonal haematopoiesis of indeterminate potential is a risk factor for Alzheimer's disease in this study. The findings of this project will shed light on the aetiology and pathogenesis of Alzheimer's disease.