Alzheimer s Disease Genetic Analysis - 1129 Words

Alzheimer’s Disease: Genetic Analysis Introduction Alzheimer’s disease (AD) is a profoundly common form of degenerative dementia that is caused by neurofibrillary tangles and amyloid plaques accumulating in the brain (Sennvik et.al., 2000). The study of the human genome has elucidated gene variants; single nucleotide polymorphisms (SNPs) and mutations which affect the age of onset and the likelihood of developing AD. Understanding the causes of familial AD, the genetic risk factors for AD and the links between AD and other disorders; such as Down’s syndrome, will aid researchers in the diagnosis and treatment of AD. Familial Alzheimer ’s disease Familial Alzheimer’s disease (FAD) is the inheritable genetic predisposition to early-onset AD.†¦show more content†¦This promotes the aggregation of amyloid plaques and causes early-onset of FAD. Presenilin 1 Presenilin 2 PSEN1 and PSEN2 are polytopic membrane proteins (Davis et.al., 1998) that form the catalytic core in the protease ÃŽ ³-secretase (Francis et.al., 2002), which is responsible for the proteolysis of APP (Navivaeva Turner, 2013). When there is a mutation at the loci for PSEN1 and PSEN2, located on chromosome 14 and 1 respectively, the activity of ÃŽ ³-secretase is altered resulting in changes in the proteolysis of APP and increased formation of AÃŽ ² (Qain et.al., 1998). Due to the increase of AÃŽ ², amyloid plaques aggregate quickly causing early-onset of AD. Amyloid Plaques and Down’s Syndrome Down’s syndrome has distinct phenotypic features which include the aggressive early-onset of AD. This is due to the location of the APP gene; on chromosome 21. The protein APP is triplicated due to the trisomy of chromosome 21 (Wisniewski et.al., 1985). The triplication of the APP gene causes an overexpression of APP; 1.5 times more protein is produced compared to persons with two copies of the APP gene. This ultimately results in high quantities of amyloid plaques due to the larger quantity of AÃŽ ² produced. Risk Factors for Alzheimer’s Disease While genetic mutations in proteins such as APP and presenilins have been revealed to cause deterministic