The genetic error causes Alzheimer's Disease to develop in the early 50s for the unfortunate family members who inherit it. On average about half of the children of someone who carries the mutation will inherit it. The mutation is extremely rare - it has only ever been found in two Swedish families and has never been found in the general population in any other countries.
The mutation had important consequences for Alzheimer's Disease research. The mutation occurs in the gene which encodes beta amyloid. Amyloid is one of the peptides which accumulate in the brains of people with Alzheimer's Disease. A great debate had existed between Alzheimer's Disease researchers about the relevance of amyloid prior to the 1990s - many scientists believed amyloid was a tombstone of the disease and was not critical to the development of the disease. However, because the only difference between the family members who developed Alzheimer's Disease and those that did not in these families was the inheritance of the mutation in the amyloid gene this suggested that the amyloid protein itself could cause the disease. The idea that amyloid could cause the disease influenced scientific research until this day. Many experimental treatments are directed towards lowering amyloid levels in the brain. The other main effect the discovery of the Swedish mutation had was to provide one transgenic mouse model of Alzheimer's Disease. Transgenic mice (e.g. Tg2576) were made which overproduce human APP with the Swedish mutation. As a consequence, the mice can develop amyloid plaques at around 13 months old.
It is thought that the Swedish mutation causes early-onset Alzheimer's disease by beta-secretase cleavage within the secretory pathway.
- Mullan M, Crawford F, Axelman K, Houlden H, Lilius L, Winblad B, Lannfelt L (August 1992). "A pathogenic mutation for probable Alzheimer's disease in the APP gene at the N-terminus of beta-amyloid". Nature Genetics. 1 (5): 345–7. PMID 1302033. doi:10.1038/ng0892-345.
- Wilson CA, Doms RW, Lee VM (August 1999). "Intracellular APP processing and A beta production in Alzheimer disease". Journal of Neuropathology and Experimental Neurology. 58 (8): 787–94. PMID 10446803. doi:10.1097/00005072-199908000-00001.
- Haass C, Lemere CA, Capell A, Citron M, Seubert P, Schenk D, Lannfelt L, Selkoe DJ (December 1995). "The Swedish mutation causes early-onset Alzheimer's disease by beta-secretase cleavage within the secretory pathway". Nature Medicine. 1 (12): 1291–6. PMID 7489411. doi:10.1038/nm1295-1291.
- Webster SJ, Bachstetter AD, Nelson PT, Schmitt FA, Van Eldik LJ (2014). "Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models". Frontiers in Genetics. 5: 88. PMC . PMID 24795750. doi:10.3389/fgene.2014.00088.