Early onset familial Alzheimer's disease

Early onset familial Alzheimer’s disease (also referred to as dominantly inherited or autosomal dominant Alzheimer's disease) is a rare genetic form of Alzheimer’s disease caused by the inheritance of mutations in one of three genes: amyloid precursor protein (APP), presenilin 1 (PSEN1), or presenilin 2 (PSEN2). It is estimated that less than 1% of all Alzheimer's disease cases are early onset familial Alzheimer's disease cases (~ 45,000 individuals are at-risk for this disease globally). Unlike the more common sporadic and late onset form of Alzheimer’s disease, individuals with these mutations start developing dementia and other disease-related symptoms usually in their 30s-50s.

In this disease, the faulty genes (or genes that contain mutations/changes in the genetic code) are passed down in an autosomal dominant fashion. For this reason, families with early onset familial Alzheimer's disease often see the disease affect multiple generations; and a parent with the disease has a 50% risk of passing on the mutation to their children.



From mutation to dementia 


How does one small change in DNA (or mutation) lead to Alzheimer's disease? Let's use an example of an actual early onset familial Alzheimer's disease mutation: p.Glu280Ala or E280A in the PSEN1 gene. In a normal PSEN1 gene, at site 280, the DNA code produces the amino acid Glutamic acid (also referred to as Glu or E). However, in a PSEN1 gene with a E280A mutation, the mutation changes the genetic code resulting in the production of the amino acid Alanine (also referred to as Ala or A). So E was exchanged for A at site 280. If the incorrect amino acid is produced this means the normal protein cannot be built, disrupting its normal function. 

Researchers have learned that disruptions in these genes (caused by the presence of a mutation) lead to an imbalance in specific proteins in the brain, namely amyloid-beta (or Abeta). This imbalance leads to an accumulation of amyloid, which forms clusters in the brain called plaques. Researchers hypothesize that the presence of amyloid plaques in the brain then initiates other events in the disease, including the formation of neurofibrillary tangles (composed of tau protein) and neuronal (or brain cell) damage, ultimately leading to dementia.


Journeys with the disease


  • How do you live knowing you might have an Alzheimer's gene?    READ

  • Alzheimer's stalks a Colombian family   READ

  • Why didn't she get Alzheimer's   READ



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  • The Genius of Marian   WATCH

  • The Alzheimer's Project   WATCH