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Alzheimer's Disease and Genetics

This strong tendency of Alzheimer's disease to run in families is due, in part, to mutations in certain genes. About five percent of all Alzheimer's disease is caused by a mutation in one of three genes, called APP, presenilin 1 (PS1), and presenilin 2 (PS2). Each of these genes is inherited in a dominant fashion. Although each mutation is different, they all occur in the same region of the gene.

APP Gene

More than 25 different mutations in the APP gene can cause early-onset Alzheimer disease. These mutations are responsible for 10 percent to 15 percent of all early-onset cases of the disorder. The APP gene provides instructions for making a protein called amyloid precursor protein. This protein is found in many tissues and organs, including the brain and spinal cord. Mutations in the APP gene can lead to an increased amount of the amyloid beta peptide or to the production of a slightly longer and stickier form of the peptide.

Certain mutations in the APP gene can also result in brain abnormalities other than Alzheimer disease. For example, a particular APP mutation causes a disorder called hereditary cerebral hemorrhage with amyloidosis-Dutch type.

PSI Gene

People with mutations in PS1 develop Alzheimer's disease at the earliest age, ranging from 29 to 62 but with an average age of 44 years. PS1 is on chromosome 14. Families with a particular PS1 mutation tend to develop Alzheimer's at the same age. Localization of PS1 immunoreactivity in familial and sporadic Alzheimer's disease suggests that genetically heterogeneous forms of the disease share a common pathophysiology involving PS1 protein.

The normal biological role of PS1 as well as the mechanism by which mutations in PS1 cause FAD remains unknown.

PS2 Gene

The PS2 gene is more rare and causes symptoms to appear between 40 and 85. Unlike the PS1 or APP genes, researchers have found people who have a mutation in the PS2 gene but did not develop Alzheimer's disease. What has been found is that the gene's mutations have been found in only six different families with Alzheimer's disease—five German families and one Italian family.The PS2 gene is required for some forms of cell death in diverse cell types.

How do we inherit out genes?

Humans inherit 23 chromosomes from each of their parents for a total of 46 chromosomes. Of these, 44 are identical in men and women, these are called autosomes. The remaining two chromosomes are called sex chromosomes, which are designated X and Y. Women inherit two X chromosomes, whereas men inherit one X chromosome from their mother and one Y chromosome from their father.

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