Researchers have developed and validated a blood-based biomarker profile with high sensitivity and specificity for Alzheimer’s disease (AD), according to a report published in the September issue of the Archives of Neurology.

Sid E. O’Bryant, PhD, from Texas Tech University Health Sciences Center in Lubbock, and colleagues in the Texas Alzheimer’s Research Consortium analyzed serum protein-based multiplex biomarker data from 197 patients diagnosed with AD and 203 control patients without AD.

Using statistical analyses, the authors created a biomarker risk score, which included levels of numerous proteins, many of which have been associated with inflammation.

“The diagnostic accuracy of the blood test is very good,” Dr. O’Bryant noted in a telephone interview withMedscape Medical News, with a sensitivity and specificity of 0.80 and 0.91, respectively, and an area under the curve of 0.91 in detecting AD. Dr. O’Bryant and several coauthors are listed on a pending patent on this biomarker algorithm.

When the investigators combined the biomarker risk score with the key clinical variables of age, sex, education, and apolipoprotein E status, the sensitivity, specificity, and area under the curve were 0.94, 0.84, and 0.95, respectively.

Table. Diagnostic Accuracy Data

Analysis AUC (95% confidence interval) Sensitivity (95% confidence interval) Specificity (95% confidence interval)
Biomarkers alone 0.91 (0.88 – 0.95) 0.80 (0.71 – 0.87) 0.91 (0.81 – 0.94)
Clinical variables alone 0.85 (0.80 – 0.91) 0.84 (0.76 – 0.90) 0.78 (0.69 – 0.85)
Biomarkers + clinical variables 0.95 (0.92 – 0.98) 0.94 (0.88 – 0.97) 0.84 (0.75 – 0.90)

According to the investigators, a “disproportionate number” of inflammatory and vascular markers were weighted most heavily in their analyses, and these markers “consistently distinguished cases from controls.”

This, they say, points to the existence of an inflammatory-related endophenotype of AD, “which could offer targeted therapeutic opportunities for this subgroup of patients.”

“A First Step” — More Study Needed, Planned

Reached for outside comment, Robert Green, MD, from Boston University School of Medicine in Massachusetts, said: “I think this is an interesting and intriguing report, but it would need to be replicated and validated in a much larger and more diverse sample of patients before any consideration of clinical use were broached.”

Dr. O’Bryant agreed. “This is a first step,” he told Medscape Medical News. “We split our sample into development and validation study, and now we have to validate it in another independent Alzheimer’s sample. A National Institutes of Health grant is currently under review for validation studies,” he noted.

Dr. O’Bryant said he plans to refine the test even further and study its value in the mild cognitive impairment group “to see if we can detect mild cognitive impairment and see if we can determine which of these patients are most likely to develop AD.”

He and his colleagues will also test the ability of the algorithm to detect AD when mixed in with non-AD dementia samples. It is possible, they note, that the inflammatory signature observed is not specific to AD but, rather, is related to other comorbid factors; namely, cardiovascular disease.

Interestingly, they note, the markers in this study have only “minimal overlap” with 18 plasma-based markers reported by another group in a “highly publicized study” in 2007; specifically, angiopoietin 2 and tumor necrosis factor. That study yielded accurate classification of cases and controls that was comparable to the serum-based panel reported in the current report (Nat Med. 2007;13:1359-1363).

“It’s likely that this differential signature profile resulted from different sample media as well as different assay platforms,” the authors conclude. Their study presents advantages over the previous work, they assert, including a larger sample size and the conduct of assays carried out by Rules-Based Medicine, “the leading biomarker company in the United States.” Their work is also unique to their knowledge, they note, in presenting serum-based findings.

This study was made possible by the Texas Alzheimer’s Research Consortium, supported by the State of Texas through the Texas Council on Alzheimer’s Disease and Related Disorders. Investigators at the University of Texas Southwestern Medical Center at Dallas also acknowledge support from a University of Texas Southwestern Alzheimer’s Disease Center National Institutes of Health, National Institute on Aging grant. A patent is being filed covering the biomarker algorithm created from this work. Dr. O’Bryant and several coauthors are listed on the patent.

Arch Neurol. 2010;67:1077-1081. Abstract


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