A Misrepresented Test Enters the Alzheimer For-Profit Market

ABSTRACT & COMMENTARY
Source: de la Monte SM, et al. Profiles of neuronal thread protein expression in Alzheimer’s disease. Ann Neurol 1992;32:733-742.

In a perversion of the conventional approach to the diagnosis of Alzheimer’s disease by exclusion of other causes of dementia, a little known spinal fluid marker test known as AD7C is being marketed as a means to "rule out Alzheimer’s disease." The test measures CSF levels of neuronal thread protein (NTP), a 21 Kilodalton protein that is reportedly increased in the cerebrospinal fluid of 88% of 500 patients with AD confirmed by autopsy. The neuronal thread protein is not known to be causally linked to Alzheimer’s disease per se, and NTP is elevated in a variety of other disorders such as brain tumors, stroke, and other neurodegenerative conditions. This lack of specificity has not deterred the Nymox Corporation from marketing the test as a means of excluding an AD diagnosis based on the assumption that a "normal" level of NTP would be unexpected in all but 12% of definite AD patients.

Clearly, NTP’s value as an Alzheimer’s diagnostic marker is limited by its lack of specificity. There is little reason to believe AD7C can be used as an exclusionary test for AD. No published information is available on the exclusionary accuracy of this test in a clinical setting. It is uncertain how levels of NTP vary over the course of Alzheimer’s disease, or whether patients in very early stages of the disease show significant NTP elevations. There is no agreement among the Alzheimer scientific and medical communities that this test is useful or that it should become part of the standard of care.

Although patients sometimes request reassurance that they are not suffering from Alzheimer’s disease, it is rarely necessary to go to the extreme of performing a lumbar puncture to confirm their normality. AD7C cannot provide certainty about the absence of Alzheimer pathology or prognosticate about the future development of the disease in an asymptomatic individual. While the test could conceivably assist in the clinical differentiation of AD from dementia secondary to depression, it has not been evaluated for this purpose and may not have sufficient sensitivity to assist in differential diagnosis in early stages of AD.

Adding insult to injury, NYMOX is charging $1000 for their AD7C testing service. A glossy brochure, a toll-free number, direct advertising to the public and other marketing strategies are being used to promote the test in the United States and other countries. The direct marketing of a such a test to the public without general acceptance by the medical and scientific community is reprehensible. The literature supplied by the company suggests that AD7C performance is similar to postmortem diagnosis where the concordance between pathology laboratories under optimal conditions is 84-92%. This is a blatant misrepresentation, since the 88% percent of AD patients reported to show NTP elevations cannot be equated with 84-92% accuracy of AD diagnosis by autopsy. We recommend that neurologists use established means to evaluate whether their patients are suffering from AD. While we may not always be able to rule out AD with certainty, we can certainly rule out the use of AD7C for this purpose. —nrr