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Posted by on May 2, 2008 in Neurology

New Biomarker for AD Highly Sensitive and Specific

New Biomarker for AD Highly Sensitive and Specific

Alzheimer’s disease isn’t particularly difficult to recognize clinically; although definitive diagnosis requires the pathologic examination of brain tissuesomething not practical in life. Nevertheless, it’s nice to have confirmation in the form of biomarkers, usually from the CSF, and particularly in cases of early disease. To this end, investigators from the University of Kentucky and the Oregon Health Sciences Center indicate that high levels of an aberrant protein complex of prostaglandin-d-synthase (PDS) and transthyretin (TTR) in CSF differentiate individuals with AD from normal control subjects. Their results were published online, April 30, in Neurology.

The conclusion was based on quantified levels of the CSF protein complex in patients who underwent autopsy and those in living individuals. The results are tabulated below:

Patient Type

Mean Age

Median Complexed TTR, ng/mL

Autopsy patients (ventricular CSF)

Normal control

83.3

<5

Diseased control

70.4

<5

Mild cognitive impairment

89.8

101.5*

Late-stage AD

81.6

74*

Living patients (archived lumbar CSF)

Normal control

71.0

<5

AD

68.4

26.5*

* P < .05.

In autopsied patients, a direct correlation was detected between the protein-complex level and measures of neurofibrillary pathology (Braak staging score) and neuritic plaque density (CERAD rating). There was, however, no significant correlation between the PDS/TTR level and the number of ApoE4 alleles.

Data from living subjects indicated that the level of CSF PDS/TTR was 100% sensitive and 93% specific for AD. Increasing PDS/TTR levels also correlated inversely with Mini-Mental State Examination scores.

It’s important to note that the study’s first 2 authors, Mark Lovell, PhD, and Bert Lynn, PhD, disclosed a financial interest in Scout Diagnostics, “a company that recently licensed intellectual property based on studies partially described in [the] report.” More specifically, the company was founded by Lovell and Lynn in 2006, along with CEO John Beran, to develop and market the diagnostic test for AD. The authors conclude that larger numbers of patients are required to confirm the utility of the CSF level of PDS/TTR for the diagnosis of AD in life.

bmartin (1127 Posts)

A native East Tennessean, Barbara Martin is a formerly practicing, board-certified neurologist who received her BS (psychology, summa cum laude) and MD from Duke University before completing her postgraduate training (internship, residency, fellowship) at the Hospital of the University of Pennsylvania in Philadelphia. She has worked in academia, private practice, medical publishing, drug market research, and continuing medical education (CME). For the last 3 years, she has worked in a freelance capacity as a medical writer, analyst, and consultant. Follow Dr. Barbara Martin on and Twitter.