Is Alzheimer’s Hereditary? Genetics Risk Factors of Alzheimer’s Disease
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
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
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
Van Cauwenberghe, C., Van Broeckhoven, C. & Sleegers, K. The genetic
landscape of Alzheimer disease: clinical implications and
perspectives. Genet Med 18, 421–430 (2016).
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).