Chromosome locations
There are 15 known gene locations identified with Alzheimer's disease. However, we know more about certain genes than others.
Early Onset Alzheimer's Disease
*Caused by point mutations:
--chromosome 21 (abnormal APP (amyloid beta 4 precursor protein))
--chromosome 14 (abnormal PSEN1 (presenilin1))
--chromosome 1 (abnormal PSEN2 (presenilin2))
*A trisomy with chromosome 21 (causes down syndrome) has also been associated with Alzheimer's disease)
*Autosomal dominant early onset AD patients have also had duplication copy number variants of the APP gene.
*The promoter region for the APP, PSEN1 and PSEN2 genes do not have a working TATA box, which is the initiation sequence for
transcription. Instead a GC sequence activates the promoter for these three genes.
--chromosome 21 (abnormal APP (amyloid beta 4 precursor protein))
--chromosome 14 (abnormal PSEN1 (presenilin1))
--chromosome 1 (abnormal PSEN2 (presenilin2))
*A trisomy with chromosome 21 (causes down syndrome) has also been associated with Alzheimer's disease)
*Autosomal dominant early onset AD patients have also had duplication copy number variants of the APP gene.
*The promoter region for the APP, PSEN1 and PSEN2 genes do not have a working TATA box, which is the initiation sequence for
transcription. Instead a GC sequence activates the promoter for these three genes.
Late Onset Alzheimer's Disease
*Caused by point mutation on chromosome 19 (APOE (apolipoprotein E))
--There are three different alleles of APOE
--APOE E2 and E3 these two alleles do not increase or decrease a persons chance of getting Alzheimer's disease
--APOE E4, the presence of this allele increases a persons chance of getting Alzheimer's disease. The chances of getting this disease increases with two copies of this allele
*APOE is the only gene associated with Alzheimer's disease whose promoter contains an active TATA box
*The APOE gene is in charge of combining fats to make lipoproteins, which are in charge of packaging cholesterol and fats and then transporting them throughout the blood stream.
--it is a part of the Very low-density lipoprotein (VLDL) which helps to remove excess cholesterol from the blood stream
--APOE E3 is the normal allele
--APOE E4 is thought to increase protein clumps or amyloid plaques in the brain (see picture below). The buildup is what causes the symptoms of Alzheimer's disease.
--There are three different alleles of APOE
--APOE E2 and E3 these two alleles do not increase or decrease a persons chance of getting Alzheimer's disease
--APOE E4, the presence of this allele increases a persons chance of getting Alzheimer's disease. The chances of getting this disease increases with two copies of this allele
*APOE is the only gene associated with Alzheimer's disease whose promoter contains an active TATA box
*The APOE gene is in charge of combining fats to make lipoproteins, which are in charge of packaging cholesterol and fats and then transporting them throughout the blood stream.
--it is a part of the Very low-density lipoprotein (VLDL) which helps to remove excess cholesterol from the blood stream
--APOE E3 is the normal allele
--APOE E4 is thought to increase protein clumps or amyloid plaques in the brain (see picture below). The buildup is what causes the symptoms of Alzheimer's disease.
Amyloid Plaques
The build up of amyloid plaques is thought to be caused by the APOE E4 allele. The buildup causes Alzheimer's symptoms.
Top Image http://archived.thebioblog.com/page/4/
Alzheimer’s disease Genetics. National Institutes of Health. (1-4). http://www.nia.nih.gov/sites/default/files/alzheimers_disease_genetics_fact_sheet.pdf (2011)
Zhang, F., Wenli, G., Hurles, M. E., Lupski, J. R. Copy Number Variation in Human Health, Disease, and Evolution. Annual Review of Genomics and Human Genetics. 10: 451-481. (2009)
Genetics home reference. Alzheimer disease. U.S. National Library of Medicine. 2013. http://ghr.nlm.nih.gov/condition/alzheimer-disease
Theuns, J. and Van Broeckhoven, C. Transcriptional regulation of Alzheimer’s disease genes: implications for susceptibility. Human Molecular Genetics. 9:2383-2394 (2000)
APOE. Genetics Home Reference. http://ghr.nlm.nih.gov/gene/APOE (2008)
Middle image http://www.dementiatoday.com/the-genetics-of-alzheimers-disease-whats-new/
Bottom image http://betastuffs.blogspot.com/2012/07/earliest-signs-of-alzheimers-disease.html
Alzheimer’s disease Genetics. National Institutes of Health. (1-4). http://www.nia.nih.gov/sites/default/files/alzheimers_disease_genetics_fact_sheet.pdf (2011)
Zhang, F., Wenli, G., Hurles, M. E., Lupski, J. R. Copy Number Variation in Human Health, Disease, and Evolution. Annual Review of Genomics and Human Genetics. 10: 451-481. (2009)
Genetics home reference. Alzheimer disease. U.S. National Library of Medicine. 2013. http://ghr.nlm.nih.gov/condition/alzheimer-disease
Theuns, J. and Van Broeckhoven, C. Transcriptional regulation of Alzheimer’s disease genes: implications for susceptibility. Human Molecular Genetics. 9:2383-2394 (2000)
APOE. Genetics Home Reference. http://ghr.nlm.nih.gov/gene/APOE (2008)
Middle image http://www.dementiatoday.com/the-genetics-of-alzheimers-disease-whats-new/
Bottom image http://betastuffs.blogspot.com/2012/07/earliest-signs-of-alzheimers-disease.html