NIHR Ask the Expert Webinar: Genetics Research

This NIHR webinar invited members of the public to ask questions of a leading specialist about the latest research into genetics.

Professor Julian Barwell answered questions in the ‘Ask the Expert’ event on the evening of Tuesday 16 May 2023. Dr Barwell is a Consultant Clinical Geneticist at the University Hospitals of Leicester NHS Trust and Honorary Professor in Genomic Medicine at the University of Leicester.

Genetics play a significant role in Alzheimer’s disease, a progressive neurodegenerative disorder that affects memory, thinking abilities, and behavior. While the exact cause of Alzheimer’s is still not fully understood, researchers have identified several genes that are associated with the development and risk of the disease.

1. Amyloid Precursor Protein (APP): Mutations in the APP gene located on chromosome 21 can lead to the production of abnormal forms of beta-amyloid proteins. These proteins can accumulate in the brain, forming plaques, which are a hallmark of Alzheimer’s disease.
2. Presenilin 1 (PSEN1): Mutations in the PSEN1 gene, located on chromosome 14, can cause early-onset familial Alzheimer’s disease. This gene provides instructions for producing a protein that is involved in the processing of APP and the production of beta-amyloid. Mutations in PSEN1 can lead to increased production of beta-amyloid, contributing to the development of the disease.
3. Presenilin 2 (PSEN2): Mutations in the PSEN2 gene, located on chromosome 1, can also cause early-onset familial Alzheimer’s disease. Similar to PSEN1, PSEN2 is involved in the processing of APP and the production of beta-amyloid.
4. Apolipoprotein E (APOE): The APOE gene, located on chromosome 19, has been widely studied in relation to late-onset Alzheimer’s disease, which is the most common form of the disease. There are three common forms, or alleles, of the APOE gene: ε2, ε3, and ε4. The ε4 allele is associated with an increased risk of developing Alzheimer’s disease and may also influence the age of onset. Individuals with one copy of the ε4 allele have a higher risk, while those with two copies have an even greater risk.

It is important to note that while these genes are associated with Alzheimer’s disease, having a mutation or a high-risk variant does not necessarily mean an individual will develop the disease. Many other factors, such as lifestyle, environment, and complex interactions between genes, also contribute to the overall risk and progression of Alzheimer’s.

Genetic testing can provide valuable information about an individual’s risk of developing Alzheimer’s disease, especially in cases of early-onset familial Alzheimer’s where the genetic cause is more apparent. However, genetic testing for late-onset Alzheimer’s is generally not recommended due to the complex nature of the disease and the limited predictive power of genetic markers alone.