Is Alzheimer’s Hereditary? Genetics Risk Factors of Alzheimer’s Disease

Date:2021-12-13
Alzheimer

Is Alzheimer’s Genetics?

Alzheimer’s disease (AD) is affected by both environmental factors and genetic factors. It has an estimated 60-80% heritability1.

APOE gene was a major gene known to increase Alzheimer’s risk. APOE gene encodes to different isoforms (APOE2, APOE3, APOE4). Each person inherits a copy of the APOE isoform from each parent. The APOE4 increases risk of both early-onset and late-onset Alzheimer’s disease. If a person has one APOE4 gene, the risk of getting Alzheimer’s disease is 3 to 4-fold of the general population. For people who have two APOE4 genes, their disease risk become 15- fold of the general population1. It is estimated that 40-65% of Alzheimer’s patients are APOE4 carriers1.

Some mutations in APP, PSEN1, and PSEN2 genes are considered to be pathogenic to Alzheimer’s disease. Mutations in APP, PSEN1, PSEN2 together explain 5-10% of early-onset cases of Alzheimer’s disease1.

Not Only a Disease for Older People

When Alzheimer’s disease occurs under age 65, it is considered to be early-onset Alzheimer’s Disease. Among all cases of Alzheimer’s Disease, there are estimated 2-10% of Alzheimer’s patients are early onset1. Around 35-60% of early-onset Alzheimer’s patients have a strong family history of Alzheimer’s disease2.

Genetics is a factor affecting the age of onset. For example, patients with the APOE4 gene tend to have an earlier onset age; and patients with PSEN1 mutation pathogenic have the most severe form of the disease, their onset age can be as early as 25 years age1.


Source:

  1. Van Cauwenberghe, C., Van Broeckhoven, C. & Sleegers, K. The genetic landscape of Alzheimer disease: clinical implications and perspectives. Genet Med 18, 421–430 (2016). https://doi.org/10.1038/gim.2015.117
  2. Porter, T., Gozt, A.K., Mastaglia, F.L. and Laws, S.M. (2019). The Role of Genetics in Alzheimer's Disease and Parkinson's Disease. In Neurodegeneration and Alzheimer's Disease (eds R. N. Martins, C.S. Brennan, W.B. Fernando, M.A. Brennan and S.J. Fuller). https://doi.org/10.1002/9781119356752.ch15