Late-onset familial Alzheimer disease

Late-onset familial Alzheimer disease

The late-onset familial form of Alzheimer disease (AD2) accounts for approximately 15–25% of all cases. These familial cases are seemingly indistinguishable from sporadic cases when observed clinically, but can be recognized based on molecular genetic testing. However, there is no clear chromosomal location for a gene directly responsible for the disease. Therefore, this complex type may involve many susceptibility genes. These familial cases are most likely due to multiple genes that make these individuals susceptible to developing the disease. For example, the APOE e4 gene on chromosome 19 associated with late-onset Alzheimer disease reduces the age in which symptoms develop by an unknown mechanism. There are many other candidate genes that are thought to modify Alzheimer disease risks and these genes, with various chromosomal locations, have been linked to the disease in different families.

Development (pathogenesis) of Alzheimer disease

Although scientists know how brain cells of persons with Alzheimer disease are affected, and additionally understand some of the genetic explanations of the disease, the precise cause of Alzheimer disease is still unclear. For example, it is known that accumulations of clumps of proteins called amyloid plaques outside brain cells and accumulation of altered proteins inside the cells called neurofibrillary tangles are characteristic of Alzheimer disease; however, it is unclear how these accumulated proteins cause brain cells to die.

According to the Alzheimer's Disease and Related Disorders Association, Inc., there are seven stages that characterize the disease:

• Stage 1: No decline in function is yet noted. This group includes individuals who may carry predictive gene mutations but have no symptoms, or those who will be affected by other unknown mechanisms.
• Stage 2: Normal function in general, although the person is aware of a subtle cognitive decline.
• Stage 3: Early Alzheimer disease. Persons experience difficulty in performing complex tasks that require cognitive skills.
• Stage 4: Mild Alzheimer disease. Persons require assistance with common tasks such as paying bills and balancing a checkbook.
• Stage 5: Moderate Alzheimer disease. Persons require assistance in making personal everyday decisions such as choosing appropriate clothing for the weather or ordering from a menu.
• Stage 6: Moderately severe Alzheimer disease. Persons require assistance dressing, bathing, and using the toilet. Urinary and bowel incontinence may be present.
• Stage 7: Severe Alzheimer disease. The vocabulary shrinks to only a few words; then little or no verbal communication is heard. The ability to walk is lost, followed by an inability to maintain a sitting posture in a chair. Eventually, the person experiences profound lack of purposeful muscle control, is totally dependent for care, and cannot smile or hold up his or her head.

Diagnosis

Alzheimer disease is diagnosed clinically by a physician, postmortem by a histopathologist (a scientist who studies diseased tissues by their various staining patterns), or genetically by identifying mutations in genes associated with the disease.

The gold standard for diagnosis of Alzheimer disease is through autopsy examination by an experienced pathologist. Detection of amyloid plaques in the brain by histopathology is the most conclusive diagnostic tool. This is performed using antibodies that bind to the particular amyloid proteins and can be visualized by microscopic evaluation, as the antibodies are tagged with a fluorescent or colorimetric molecule. A positive result would involve a significantly greater number of plaques compared to agematched controls. Other brain defects that characterize the disease, such as abnormal nerve cell configurations called intraneuronal neurofibrillary tangles, can also be detected by histopathology by the same methods. A clinical diagnosis by a physician accounts for 80–90% of patients diagnosed with Alzheimer disease.