Dementia: Update for the Practitioner

Genetics of Neurodegenerative Disease: Alzheimer's Disease, Frontotemporal Dementia
Jennifer Williamson-Catania, M.S.

Family Patterns in Alzheimer's Disease

Our understanding of the genetics of neurodegenerative disease is expanding all the time. There are many diseases for which we can test, and of these I will focus on Alzheimer's disease (AD) and frontotemporal dementia.

When I take a family history of a patient, I look at the pattern of inheritance and onset of the disease within a family. I try to distinguish whether a family is exhibiting late-onset AD or early-onset AD, and whether the disease is sporadic or familial. This sounds simple, but it is often very difficult to identify a family history of AD because family members may die from competing causes of death and may not live long enough to develop the disease. Also, and members of the previous generation may not have had a clear diagnosis of dementia or Alzheimer's disease.

Late-onset AD is commonly defined by onset of symptoms at age 65 or older. Early-onset AD is sometimes classified as beginning by age 60, sometimes below age 65. Sporadic disease is defined as occurrence in one individual in a family, and familial disease involves two or more individuals. In early-onset disease, we can see an autosomal-dominant pattern of inheritance in families, with multiple generations affected as the disease is passed from parent to child.

Four genes have been identified as playing a role in AD: APOE, APP, PS1, and PS2. Three additional loci have been identified on chromosomes 9, 10, and 12. The attributable risk, or genetic risk, of developing AD can be explained by some of the genes already identified as being involved, but there is clearly a lot that we do not know. Research is ongoing to find other genes that may be associated, in particular with late-onset Alzheimer's disease.


	Risk Factors for Alzheimer's Disease
	Family history of AD Strongest association in the first-degree relatives 2-3 fold increase in risk Higher with each additional relative
	Genetics four genes identified APOE, APP, PS1, PS2 three additional loci Chromosomes 9, 10, & 12
	Factors that modify genetic risk age of individual gender ethnicity
	Environmental factors head trauma fewer years of formal education

	There are a number of risk factors for Alzheimer's disease. Courtesy of Jennifer Williamson-Catania, M.S.


	Alzheimer's Disease Genetics


	Four genes have been identified as related to a genetic risk of developing AD, and research is ongoing to find others. Courtesy of Jennifer Williamson-Catania, M.S.


	Risk Factors for AD

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