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Cerebrospinal fluid (CSF) proteins & Mild cognitive impairment (MCI)

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Cerebrospinal fluid (CSF) proteins

CSF is a clear fluid that bathes and cushions the brain and spinal cord. Adults have about 1 pint of CSF, which physicians can sample through a minimally invasive procedure called a lumbar puncture, or spinal tap. Research suggests that Alzheimer's disease in early stages may cause changes in CSF levels of tau and beta-amyloid, two proteins that form abnormal brain deposits strongly linked to Alzheimer's.

One challenge researchers face is that analysis of protein levels in the same sample often varies significantly from institution to institution. Achieving consistent measurement is a barrier that has been overcome in other medical conditions by using a standard procedure protocol and comparing results from the same sample at multiple sites designated as reference laboratories.

Blood and urine tests

Researchers are also investigating whether Alzheimer's disease causes consistent, measurable changes in urine or blood levels of tau, beta-amyloid or other biomarkers before symptoms appear. In addition, scientists are exploring whether early Alzheimer's leads to detectable changes elsewhere in the body, such as the lens of the eye.

Genetic risk profiling

Scientists have identified three genes with rare variations that cause Alzheimer's and several genes that increase risk but don't guarantee that a person will develop the disease. Investigators worldwide are working to find additional risk genes. As more effective treatments are developed, genetic profiling may become a valuable risk assessment tool for wider use.

Genetic testing for APOE-e4, the strongest risk gene, is included in some clinical trials to identify participants at high risk for the disease. APOE-e4 testing is not currently recommended outside research settings because there are no treatments yet available that can change the course of Alzheimer's. Learn more about genetics and Alzheimer's disease.

Mild cognitive impairment (MCI)

Research has shown that individuals with MCI have a significantly increased risk of developing Alzheimer's disease within a few years, compared to people with normal cognitive function; research surrounding MCI offers another potential path to earlier diagnosis.

Individuals with MCI have a problem with memory or another mental function serious enough to be noticeable to themselves and those close to them and to show up on mental status testing. These problems, however, are not severe enough to interfere with daily activities, and so the person does not meet current diagnostic criteria for Alzheimer's or another dementia.

Although individuals with MCI may go on to develop Alzheimer's disease, this is not always the case. In some people, MCI never gets worse. In others, it eventually gets better.

Investigators are trying to answer the following questions to increase MCI's usefulness as a diagnostic category:

How should we standardize the definition of MCI?
What are the best mental status tests to detect the earliest changes in memory and other cognitive areas?
What biological changes are associated with MCI?
Which individuals with MCI will progress to Alzheimer's disease or another dementia?

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