Alzheimer's (Genetics)

Question 1

Early onset Alzheimer’s

Answer 1

Take note that early onset (familial) Alzheimer’s (EOFAD) is very rare and account for only 0.1% of all Alzheimer’s cases.

There are 3 genes of importance:-

amyloid precursor protein (APP) - accounts for 10-15% of EOFAD
presenilin one (PSEN-1) - accounts for 30-70% of EOFAD
presenilin two (PSEN-2) - accounts for 5% of EOFAD

The APP gene is located on chromosome 21 and codes for the production of amyloid precursor protein. Little is known about the function of this protein other than that it’s a precursor of amyloid.

The presenilins are components of enzymes that cleave APP to produce amyloid beta fragments of different lengths. Alterations in the ratios of these fragments can result in insoluble amyloid leading to plaque formation. The PSEN-1 gene is located on chromosome 14 and the PSEN-2 gene on chromosome 1. The presenilins account for the majority of early onset Alzheimer’s cases.

Question 2

Late onset Alzheimer’s

Answer 2

Only one gene has been identified for late onset cases, apolipoprotein E (APOE).

APOE is thought to be involved in the breakdown of amyloid plaques and different forms of it seem to vary in how effective they can do this. The gene is on chromosome 19 and has three alleles, APOE2, APOE3, and APOE4. The E4 variant is the risk factor for late onset Alzheimer’s. People homozygous for the E4 allele have between a 10 and 30 times increased risk for Alzheimer’s compared to people not carrying any E4 alleles. Heterozygotes for APOE4 have a 3 times increased risk. In addition each E4 allele lowers the age of onset by 10 years.

APOE2 - protective
APOE3 - neutral
APOE4 - increases risk

Question 3

Alzheimer’s and Down’s syndrome

Answer 3

People with Down’s syndrome are at high risk of developing Alzheimer’s disease. This is thought to be due to the fact that they inherit an extra copy of the amyloid precursor protein (APP) located on chromosome 21.
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