MAPT Gene

Frontotemporal dementia with parkinsonism-17 (FTDP-17) is a brain disorder. It is part of a group of conditions, called frontotemporal dementia or frontotemporal degeneration, that are characterized by a loss of nerve cells (neurons) in areas of the brain called the frontal and temporal lobes. Over time, a loss of these cells can affect personality, behavior, language, and movement.

The signs and symptoms of FTDP-17 usually become noticeable in a person's forties or fifties. Most affected people survive 5 to 10 years after the appearance of symptoms, although a few have survived for two decades or more.

Changes in personality and behavior are often early signs of FTDP-17. These changes include a loss of inhibition, inappropriate emotional responses, restlessness, neglect of personal hygiene, and a general loss of interest in activities and events. The disease also leads to deterioration of cognitive functions (dementia), including problems with judgment, planning, and concentration. Some people with FTDP-17 develop psychiatric symptoms, including obsessive-compulsive behaviors, strongly held false beliefs (delusions), and false perceptions (hallucinations). It may become difficult for affected individuals to interact with others in a socially appropriate manner. They increasingly require help with personal care and other activities of daily living.

Many people with FTDP-17 develop problems with speech and language. They may have trouble finding words, confuse one word with another (semantic paraphasias), and repeat words spoken by others (echolalia). Difficulties with speech and language worsen over time, and most affected individuals eventually lose the ability to communicate.

FTDP-17 is also characterized by problems with movement that worsen over time. Many affected individuals develop features of parkinsonism, including tremors, rigidity, and unusually slow movement (bradykinesia). As the disease progresses, most affected individuals become unable to walk. Some people with FTDP-17 also have restricted up-and-down eye movement (vertical gaze palsy) and rapid abnormal movements of both eyes (saccades).

Parkinson disease is a progressive disorder of the nervous system. The disorder affects several regions of the brain, especially an area called the substantia nigra that controls balance and movement.

Often the first symptom of Parkinson disease is trembling or shaking (tremor) of a limb, especially when the body is at rest. Typically, the tremor begins on one side of the body, usually in one hand. Tremors can also affect the arms, legs, feet, and face. Other characteristic symptoms of Parkinson disease include rigidity or stiffness of the limbs and torso, slow movement (bradykinesia) or an inability to move (akinesia), and impaired balance and coordination (postural instability). These symptoms worsen slowly over time.

Parkinson disease can also affect emotions and thinking ability (cognition). Some affected individuals develop psychiatric conditions such as depression and visual hallucinations. People with Parkinson disease also have an increased risk of developing dementia, which is a decline in intellectual functions including judgment and memory.

Generally, Parkinson disease that begins after age 50 is called late-onset disease. The condition is described as early-onset disease if signs and symptoms begin before age 50. Early-onset cases that begin before age 20 are sometimes referred to as juvenile-onset Parkinson disease.

Progressive supranuclear palsy is a brain disorder that affects movement, vision, speech, and thinking ability (cognition). The signs and symptoms of this disorder usually become apparent in mid- to late adulthood, most often in a person's 60s. Most people with progressive supranuclear palsy survive 5 to 9 years after the disease first appears, although a few affected individuals have lived for more than a decade.

Loss of balance and frequent falls are the most common early signs of progressive supranuclear palsy. Affected individuals have problems with walking, including poor coordination and an unsteady, lurching gait. Other movement abnormalities develop as the disease progresses, including unusually slow movements (bradykinesia), clumsiness, and stiffness of the trunk muscles. These problems worsen with time, and most affected people ultimately require wheelchair assistance.

Progressive supranuclear palsy is also characterized by abnormal eye movements, which typically develop several years after the other movement problems first appear. Restricted up-and-down eye movement (vertical gaze palsy) is a hallmark of this disease. Other eye movement problems include difficulty opening and closing the eyelids, infrequent blinking, and pulling back (retraction) of the eyelids. These abnormalities can lead to blurred vision, an increased sensitivity to light (photophobia), and a staring gaze.

Additional features of progressive supranuclear palsy include slow and slurred speech (dysarthria) and trouble swallowing (dysphagia). Most affected individuals also experience changes in personality and behavior, such as a general loss of interest and enthusiasm (apathy). They develop problems with cognition, including difficulties with attention, planning, and problem solving. As the cognitive and behavioral problems worsen, affected individuals increasingly require help with personal care and other activities of daily living.