1. SECTIONS:
2. preface & acknowledgements
3. genetics at a glance
4. contacts, support & testing
5. testing & pregnancy
6. newborn screening
7. cancer in the family
8. cardiovascular conditions
9. chromosomal conditions
10. clotting & bleeding conditions
11. cystic fibrosis
12. diabetes
13. fragile X syndrome and other causes of developmental delay
14. haemoglobinopathies
15. hereditary haemochromatosis
16. neurofibromatosis
17. neurological conditions
18. psychiatric conditions
19. genetics in practice
20. emerging genetic technologies
21. glossary

Late-onset familial Alzheimer disease (LoFAD)

 

Clinical features

1. Typically has an onset >65 years and is indistinguishable from non-familial late-onset Alzheimer disease.

 

Genetics

1. No single causative genes have been recognised for LoFAD.
   
2. A susceptibility gene, ApoE, which has three forms (alleles) - ApoE2, ApoE3 and ApoE4 - has been identified for Alzheimer disease.
3. An individual’s risk of developing late-onset Alzheimer disease is related to the combination of ApoE alleles they carry
   
4. Those individuals with one or two copies of the ApoE4 allele are at increased risk of developing
   Alzheimer disease
   
5. However, 50% of all people with late-onset Alzheimer disease do not have a copy of ApoE4. It is possible to have this form of the gene and not develop dementia despite living to old age

 

Prevalence

1. The prevalence of dementia in individuals over the age of 85 years is estimated to be 25 to 45%.
   
2. Approximately 10% of all persons over the age of 70 years have significant memory loss and more than
   half of these individuals have Alzheimer disease.
   
3. About 25% of all Alzheimer disease is familial.
   
4. About 1 to 6% of all Alzheimer disease is early-onset (<60 years) and about 60% of EoFAD.
   
5. LoFAD is responsible for up to 10% of late-onset cases.

 

Investigations

1. Predictive genetic testing is available for at-risk relatives of individuals identified with EoFAD due to mutations in PS-1, APP and PS-2.
2. However, the testing is only available when a specific mutation has been identified in an affected
   family member
3. Testing for ApoE status for Alzheimer disease has been the subject of debate. To date, local collaborative
   groups and international bodies have recommended that ApoE not be used for diagnostic or predictive
   testing for Alzheimer disease.

 

Management

1. Refer to neurogenetics or Genetics Services for the following:
2. Any individual with a personal or family history consistent with early-onset familial Alzheimer disease
   (see Criteria for EoFAD’).
   
3. Any individual with two or more affected family members with late-onset Alzheimer disease over one
   generation within the same parental line.
   
4. While ApoE testing for Alzheimer disease risk is not recommended, individuals requesting ApoE
   testing for Alzheimer disease risk may benefit from referral to a neurogenetics clinic for further discussion.

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