Is Alzheimer’s disease hereditary?

Familial Alzheimer’s disease (FAD) is an inherited, rare form of the disease, affecting less than 10 percent of Alzheimer’s disease patients. FAD develops before age 65, in people as young as 35. It is caused by one of three gene mutations on chromosomes 1, 14 and 21. If even one of these mutated genes is inherited from a parent, the person will almost always develop FAD. All offspring in the same generation have a 50/50 chance of developing FAD if one parent has it.

The majority of Alzheimer’s disease cases are late-onset, usually developing after age 65. Late-onset Alzheimer’s disease has no known cause and shows no obvious inheritance pattern. However, in some families, clusters of cases are seen. Although a specific gene has not been identified as the cause of late-onset Alzheimer’s disease, genetic factors do appear to play a role in the development of this form of the disease. A gene called Apolipoprotein E (ApoE) appears to be a risk factor for the late-onset form of AD. There are three forms of this gene: ApoE2, ApoE3 and ApoE4. Roughly one in four Americans has ApoE4 and one in twenty has ApoE2. While inheritance of ApoE4 increases the risk of developing AD, ApoE2 substantially protects against the disease.

Scientists believe that several other genes may influence the development of Alzheimer’s disease. Two of these genes, UBQLN1 and SORL1, are located on chromosomes 9 and 11. Researchers have also identified three genes on chromosome 10, one of which produces an insulin degrading enzyme that may contribute to the disease. A gene, called TOMM40, appears to significantly increase one’s susceptibility to developing Alzheimer’s when other risk factors are present, such as having the ApoE-4 gene. Several recently discovered genes that influence Alzheimer’s disease risk are CLU (also called APOJ) on chromosome 8, which produces a protein called clusterin, PICALM on chromosome 11 and CR1 on chromosome 1.

In October of 2013, an international group of researchers reported on the identification of 11 new genes that offer important new insights into the disease pathways involved in Alzheimer’s disease. The new genes (HLA-DRB5/HLA0DRB1, PTK2B, SLC24A4-0RING3, DSG2, INPP5D, MEF2C, NME8, ZCWPW1, CELF1, FERMT2 and CASS4) add to a growing list of gene variants associated with onset and progression of late-onset Alzheimer’s.

Genetic risk factors alone are not enough to cause the late-onset form of Alzheimer’s disease, so researchers are actively exploring education, diet and environment to learn what role they might play in the development of this disease.