The nucleus of almost every human cell contains a “blueprint” that carries the instructions a cell needs to do its job. The blueprint is made up of DNA (deoxyribonucleic acid), which is present in long strands that would stretch to nearly 6 feet in length if attached end to end.

The DNA is packed tightly together with proteins into compact structures called chromosomes. Normally, each cell has 46 chromosomes in 23 pairs, which are inherited equally from a father and a mother. The DNA in nearly all cells of an individual is identical. Each chromosome contains many thousands of segments, called genes.

People inherit two copies of each gene from their parents, except for genes on the X and Y chromosomes, which, among other functions, determine a person’s sex. The genes “instruct” the cell to make unique proteins that, in turn, dictate the types of cells made. Genes also direct almost every aspect of the cell’s construction, operation, and repair.

Even slight changes in a gene can produce a protein that functions abnormally, which may lead to disease. Other changes in genes may increase or decrease a person’s risk of developing a particular disease.

https://www.nia.nih.gov/health/alzheimers-disease-genetics-fact-sheet

Alzheimer’s disease is either early onset or late onset and both have a genetic component

EARLY ONSET ALZHEIMER’S DISEASE

This rare form of Alzheimer’s disease affects people age 30 to 60. The majority cases of this type of Alzheimer’s disease are inherited a type called familial Alzheimer disease (FAD).

Deterministic genes will directly cause a disease, guaranteeing that anyone who inherits them will develop the disorder. Scientists have discovered variations that directly cause Alzheimer’s disease in the genes coding three proteins: amyloid precursor protein (APP, located on chromosome 21), presenilin-1 (PS-1 located on chromosome 14) and presenilin-2 (PS-2 located on chromosome 1).

Mutations of these genes cause the production of excessive  amounts of a toxic protein fragment called amyloid-beta peptide.

The prevalence of the defective versions of these genes is as follows:

More than 80 known families worldwide have a mutation in the APP gene on chromosome 21, which affects production of the protein amyloid. A build-up of amyloid in the brain has been linked to Alzheimer’s disease.

Nearly 400 known families worldwide carry a mutation in the PSEN-1 gene on chromosome 14. This causes up to half of all early onset familial Alzheimer’s disease, with first symptoms from as early as 30 years of age.

Only a few dozen known families (mainly resident in the United States) have a mutation in PSEN-2 on chromosome 1, causing early onset familial Alzheimer’s disease that starts slightly later than for PSEN-1.  

LATE ONSET ALZHEIMER’S DISEASE

Risk genes increase the likelihood of developing a disease, but do not guarantee it will happen. Scientists have so far identified several risk genes implicated in Alzheimer’s disease.

The gene with the greatest known influence on the risk of developing late onset Alzheimer’s disease is called apolipoprotein E (APOE). This gene is found on chromosome 19. APOE-e4 is one of three common forms of the APOE gene; the others are APOE-e2 and APOE-e3.

Every person in the world carries two Apolipoprotein genes: they can be the same type (2,2; 3,3 or 4,4), or a mixture of two types (2,3; 2,4; 3,4).

APOE-e4 is associated with a higher risk of Alzheimer’s. About a quarter of the general population inherits one copy of the APOE-e4 gene. This increases their lifetime risk of developing Alzheimer’s disease by up to four times.

About 2 per cent of the population gets a ‘double dose’ of the APOE-e4 gene – one from each parent. This increases their risk of developing Alzheimer’s disease by about 10 times or more. However, even then, they are not certain to develop Alzheimer’s.

About 60 per cent of the population has a ‘double dose’ of the APOE-e3 gene and is at ‘average’ risk. Up to half of this group develops Alzheimer’s disease by their late 80s.

The APOE-e2 form of the gene is mildly protective against Alzheimer’s: people with it are slightly less likely to develop the disease. In the general population, 11 per cent has one copy of APOE-e2 together with a copy of APOE-e3., and one in 200 (0.5 per cent) has two copies of APOE-e2

Some researchers think that APOE-e4 does not affect whether a person will get Alzheimer’s disease but the age at which they get it. This suggests that people with APOE-e4 are likely to develop the disease before people with APOE-e2.

Until recently, APOE was the only gene to be consistently linked to the risk of late onset Alzheimer’s disease.  However in 2009 nine more genes were  identified as having links to Alzheimer disease.

2013: Scientists identified 11 new genes associated with the disease:.  Nature Genetics on October 27, 2013

The findings strengthen evidence about the involvement of certain pathways in Alzheimer’s disease, including the immune response, inflammation, cellular protein trafficking, and lipid transport.

SOURCES:

http://www.alzheimers.org.uk/factsheet/405

http://www.fightdementia.org.au/understanding-dementia/dementia–heredity.aspx

https://www.alz.org/alzheimers_disease_causes_risk_factors.asp

http://www.nih.gov/researchmatters/november2013/11042013alzheimer.htm

http://www.nia.nih.gov/alzheimers/publication/alzheimers-disease-genetics-fact-sheet