Alzheimer's Disease Markers


Alzheimer’s Disease Markers

Synonym/acronym: CSF tau protein and β-amyloid-42, AD, APP, PS-1, PS-2, Apo E4.

Common use

To assist in diagnosing Alzheimer’s disease and monitoring the effectiveness of therapy.

Specimen

Cerebrospinal fluid (CSF) (2 mL) collected in a plain plastic conical tube for tau protein and β-amyloid-42; whole blood from one full lavender-top (EDTA) tube for apolipoprotein E4 (ApoE4) genotyping, β-amyloid precursor protein, presenilin 1, and presenilin 2.

Normal findings

(Method: Enzyme-linked immunosorbent assay) Simultaneous tau protein and β-amyloid-42 measurements in CSF are used in conjunction with detection of apolipoprotein E4 alleles (restriction fragment length polymorphism) and identification of mutations in the β-amyloid precursor protein (APP), presenilin 1 (PS-1) and presenilin 2 (PS-2) genes (polymerase chain reaction and DNA sequencing) as biochemical and genetic markers of Alzheimer’s disease (AD). Scientific studies indicate that a combination of elevated tau protein and decreased β-amyloid-42 protein levels are consistent with the presence of AD. The testing laboratory should be consulted for interpretation of results.

Description

AD is the most common cause of dementia in the elderly population. AD is a disorder of the central nervous system (CNS) that results in progressive and profound memory loss followed by loss of cognitive abilities and death. It may follow years of progressive formation of β-amyloid plaques and brain tangles, or it may appear as an early-onset form of the disease. Two recognized pathologic features of AD are neurofibrillary tangles and amyloid plaques found in the brain. Abnormal amounts of the phosphorylated microtubule-associated tau protein are the main component of the classic neurofibrillary tangles found in patients with AD. Tau protein concentration is believed to reflect the number of neurofibrillary tangles and may be an indication of the severity of the disease. β-Amyloid-42 is a free-floating protein normally present in CSF. It is believed to accumulate in the CNS of patients with AD, causing the formation of amyloid plaques on brain tissue. The result is that these patients have lower CSF values than age-matched healthy control participants. The study of genetic markers of AD has led to an association between an inherited autosomal dominant mutation in the APP, PS-1, and PS-2 genes and overproduction of amyloid proteins. Mutations in these genes are believed to be responsible for some cases of early-onset AD. An association also exists between a gene that codes for the production of ApoE4 and development of late-onset AD. Diagnosis of AD includes a thorough physical examination, a complete medical history, neurological examination, tests of mental status, blood tests, and brain imaging procedures.

This procedure is contraindicated for

  • high alert Patients with infection present at the needle insertion site.
  • high alert Patients with degenerative joint disease or coagulation defects.
  • high alert Patients who are uncooperative during the procedure.
  • high alert Patients with increased intracranial pressure because overly rapid removal of CSF can result in herniation.

Indications

  • Assist in establishing a diagnosis of AD

Potential diagnosis

Increased in

  • Tau protein is increased in AD.

  • Presence of ApoE4 alleles is a genetic risk factor for AD.

  • Identification of mutations in the APP, PS-1, and PS-2 genes is associated with forms of AD.

Decreased in

    β-Amyloid-42 is decreased in up to 50% of healthy control participants.

    AD (related to accumulation in the brain with a corresponding decrease in CSF) Creutzfeldt-Jakob disease

Critical findings

    N/A

Interfering factors

  • Some patients with AD may have normal levels of tau protein because of an insufficient number of neurofibrillary tangles.

Nursing Implications and Procedure

Pretest

  • Positively identify the patient using at least two unique identifiers before providing care, treatment, or services.
  • Patient Teaching: Inform the patient this test can assist in diagnosing AD and/or evaluating the effectiveness of medication used to treat AD.
  • Obtain a history of the patient’s complaints, including a list of known allergens, especially allergies or sensitivities to latex or anesthetics.
  • Obtain a history of the patient’s neurological system, symptoms, and results of previously performed laboratory tests and diagnostic and surgical procedures.
  • Obtain a list of the patient’s current medications, including herbs, nutritional supplements, and nutraceuticals (see Effects of Natural Products on Laboratory Values online at DavisPlus).
  • Review the procedure with the patient. Inform the patient that the procedure will be performed by a health-care provider (HCP) trained to perform the procedure and takes approximately 20 min. Address concerns about pain and explain that there may be some discomfort during the lumbar puncture. Inform the patient that a stinging sensation may be felt as the local anesthetic is injected. Instruct the patient to report any pain or other sensations that may require repositioning of the spinal needle.
  • Inform the patient that the position required for the lumbar puncture may be awkward but that someone will assist. Stress the importance of remaining still and breathing normally throughout the procedure.
  • Sensitivity to social and cultural issues, as well as concern for modesty, is important in providing psychological support before, during, and after the procedure.
  • Note that there are no food, fluid, or medication restrictions unless by medical direction.
  • Make sure a written and informed consent has been signed prior to the procedure and before administering any medications.

Intratest

  • Potential complications:

  • Headache is a common minor complication experienced after lumbar puncture and is caused by leakage of the spinal fluid from around the puncture site. On a rare occasion the headache may require treatment with an epidural blood patch in which an anesthesiologist or pain management specialist injects a small amount of the patient’s blood in the epidural space of the puncture site. The blood patch forms a clot and seals the puncture site to prevent further leakage of CSF and provides relief within 30 minutes. Other complications include lower back pain after the procedure, bleeding near the puncture site, or brain stem herniation, due to increased intracranial pressure.

  • Avoid the use of equipment containing latex if the patient has a history of allergic reaction to latex.
  • Instruct the patient to cooperate fully and to follow directions. Direct the patient to breathe normally and to avoid unnecessary movement.
  • Observe standard precautions, and follow the general guidelines in Patient Preparation and Specimen Collection. Positively identify the patient, and label the appropriate specimen container with the corresponding patient demographics, initials of the person collecting the specimen, date, and time of collection.
  • Record baseline vital signs, and assess neurological status. Protocols may vary among facilities.
  • To perform a lumbar puncture, position the patient in the knee-chest position at the side of the bed. Provide pillows to support the spine or for the patient to grasp. The sitting position is an alternative. In this position, the patient must bend the neck and chest to the knees.
  • Prepare the site (usually between L3 and L4 or L4 and L5) with povidone-iodine, and drape the area.
  • Inject a local anesthetic. Using sterile technique, the HCP inserts the spinal needle through the spinous processes of the vertebrae and into the subarachnoid space. Needle size has been shown to play a significant role in predictable incidence of postpuncture headache. However, the smaller the bevel, the more time is required to collect a sufficient volume of fluid; usually a 22–g needle is used. The stylet is removed. CSF drips from the needle if it is properly placed.
  • Attach the stopcock and manometer, and measure initial CSF pressure. Normal pressure for an adult in the lateral recumbent position is 60–200 mm H2O, and 10–100 mm H2O for children less than 8 yr. These values depend on the body position and are different in a horizontal or sitting position. CSF pressure may be elevated if the patient is anxious, holding his or her breath, tensing muscles, or if the patient’s knees are flexed too firmly against the abdomen. CSF pressure may be significantly elevated in patients with intracranial tumors or space occupying pockets of infection as seen in meningitis.
  • If the initial pressure is elevated, the HCP may perform Queckenstedt’s test. To perform this test, apply pressure to the jugular vein for about 10 sec. CSF pressure usually rises in response to the occlusion, then rapidly returns to normal within 10 sec after the pressure is released. Sluggish response may indicate CSF obstruction.
  • Obtain four (or five) vials of fluid, according to the HCP’s request, in separate tubes (1 to 3 mL in each), and label them numerically (1 to 4 or 5) in the order in which they were filled. Take a final pressure reading, and remove the needle. Clean the puncture site with an antiseptic solution, and apply direct pressure with dry gauze to stop bleeding or CSF leakage. Observe/assess puncture site for bleeding, CSF leakage, or hematoma formation, and secure gauze with adhesive bandage.
  • Promptly transport the specimen to the laboratory for processing and analysis.

Post-Test

  • Inform the patient that a report of the results will be made available to the requesting HCP, who will discuss the results with the patient.
  • Monitor vital signs and neurologic status every 15 min for 1 hr, then every 2 hr for 4 hr, and as ordered after lumbar puncture. Take the temperature every 4 hr for 24 hr. Compare with baseline values. Protocols may vary among facilities.
  • Administer fluids if permitted, especially fluids containing caffeine, to replace lost CSF and help prevent or relieve headache, which is a side effect of lumbar puncture. Advise the patient that headache may begin within a few hours up to 2 days after the procedure and may be associated with dizziness, nausea, and vomiting. The length of time for the headache to resolve varies considerably.
  • Observe/assess the puncture site for leakage, and frequently monitor body signs, such as temperature and blood pressure.
  • Position the patient flat, either on the back or abdomen, although some HCPs allow 30 degrees of elevation. Maintain this position for 8 hr. Changing position is acceptable as long as the body remains horizontal.
  • Observe/assess the patient for neurological changes, such as altered level of consciousness, change in pupils, reports of tingling or numbness, and irritability.
  • Recognize anxiety related to test results, and be supportive of perceived loss of independence and fear of shortened life expectancy. Discuss the implications of abnormal test results on the patient’s lifestyle. Provide teaching and information regarding the clinical implications of the test results, as appropriate. Educate the patient and family members regarding access to counseling and other supportive services. Provide contact information, if desired, for the Alzheimer’s Association (www.alz.org).
  • Reinforce information given by the patient’s HCP regarding further testing, treatment, or referral to another HCP. Answer any questions or address any concerns voiced by the patient or family.
  • Depending on the results of this procedure, additional testing may be performed to evaluate or monitor progression of the disease process and determine the need for a change in therapy. Evaluate test results in relation to the patient’s symptoms and other tests performed.

Related Monographs

  • Related tests include CT brain, evoked brain potentials, MRI brain, and FDG-PET scan.
  • See the Musculoskeletal System table at the end of the book for related tests by body system.