Risk factors increase the likelihood of disease occurring. They do not inevitably cause dementia, but have a strong association. Some risk factors can be modified by changing lifestyle behaviours, while others – such as family history, age or genetic makeup – cannot be changed.

The genes that seem most significant in diseases that cause dementia are those linked to the aggregation of proteins, which leads to the death of neurons.

A family history of dementia is a risk factor for Alzheimer’s. Younger-onset Alzheimer’s is largely inherited and most cases can be traced to mutations in one of three genes: amyloid precursor protein (APP), presenilin 1 (PSEN1) or presenilin 2 (PSEN2). The presence of one or more of these mutated genes virtually guarantees the development of dementia. Mutations of these genes promote the production of toxic amyloid-ß plaques. If these are inherited, a person will almost certainly develop the disease. However, some people still develop younger-onset Alzheimer’s even without these genes.

Alzheimer's disease risk genes

For the most common form – late-onset Alzheimer’s disease – a variant of the apolipoprotein E (ApoE) gene known as ApoE 4 increases the risk. People with one copy of ApoE 4 are about three times more likely to develop the disease, and those with two copies of ApoE 4 form are about five to eight times more likely to succumb. 

Half or more of people with Alzheimer’s disease have at least one copy of the ApoE 4 gene – but while it means that the chances are higher of developing the disease, it is not inevitable. 

Everyone receives two copies of the ApoE gene, one from your mother and the other from your father. ApoE has three common variants and you can inherit any two of these: 

•  ApoE 2 – rare, and may protect against Alzheimer’s

•  ApoE 3 – common and seems to play a neutral role

•  ApoE 4 – the risk gene. One copy increases the risk 3-fold. Two copies increases the risk 5-8-fold.

Genetic risk factors of Alzheimer's disease

Studies have identified about a dozen other genes that may increase the risk of developing Alzheimer’s. However, the known contribution of genetics in causing Alzheimer’s disease – combining young-onset and late-onset forms – remains small.

The genetic contribution to other dementias is also relatively minor. About 10% of dementia with Lewy bodies cases are inherited. And in frontotemporal dementia, about 10-15% of cases are inherited, while a further 25% have a family history of neurodegenerative disease.