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 tissue—something 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.
