Causes and symptoms---etc

Causes and symptoms

Although there are several known causes of Alzheimer disease, about 75% of cases are sporadic and occur without a clear cause; this percentage represents people without a family history of the disorder. Scientists assume that these cases are due to a combination of unknown genetic predisposing factors and environmental exposures. Although various narcotics, therapeutic drugs, viruses, and toxins have been implicated in the etiology of the disease, there is currently no proof that they can cause Alzheimer disease.

Genetic basis for Alzheimer disease

Of all persons with Alzheimer disease, up to 25% of cases are thought to be part of a familial-based inheritance pattern and therefore are only determined based on family history or genetic test results. In general, these forms of Alzheimer disease are inherited as an autosomal dominant disorder, meaning that affected individuals have a 50% chance of passing on the mutated gene to their offspring in each pregnancy. There is a late-onset familial form (AD2), three early-onset familial forms (AD1, AD3, AD4), and a form of Alzheimer disease associated with Down syndrome.

Down syndrome and Alzheimer disease

Less than 1% of all cases of Alzheimer disease are due to a chromosomal defect called trisomy 21 (also known as Down syndrome). This occurs when there are three copies of genes found on chromosome 21, usually due to a person having an extra chromosome 21. These individuals usually develop Alzheimer disease after the age of 40. The APP gene, which encodes the amyloid precursor protein and is implicated in the pathogenesis of Alzheimer disease, is localized to chromosome 21; it is felt that people with Down syndrome overproduce this protein, resulting in its accumulation in the brain. The excess protein is thought to cause the disease.

Early-onset familial Alzheimer disease

A low percentage (2%) of Alzheimer cases results from a familial form of the disease in which there is an early onset of symptoms (AD1, AD3, and AD4), usually occurring before the age of 60. Age of onset usually occurs around 40–50 years, but can occur as early as 30 yea majority of these persons have family members that are also affected. The clinical manifestations are similar to the adult-onset form, with loss of memory and cognitive ability. In this form of Alzheimer disease, there are several chromosomal locations of genes implicated in causing the disease.

AD1 accounts for approximately 10–15% of earlyonset Alzheimer disease and involves a protein called presenilin 1 that has a mutation in the gene that encodes it called PSEN1, which is found on chromosome 14. AD3 accounts for 20–70% of the early-onset familial form and is caused by mutations in APP found on chromosome 21, which encodes a protein called amyloid beta A4. AD4 is extremely rare and is caused by mutations in PSEN2, localized to chromosome 1, and encodes a protein called presenilin 2.