Spinal Fluid Tests Differentiate Concurrent Brain Diseases

Alzheimer's disease (AD) can be distinguished from frontotemporal lobar degeneration (FTLD) by looking at the levels of two specific biomarkers in the spinal fluid.

By using different platforms and assaying the concentration of a neuronal protein and peptide amino acids in cerebral spinal fluid (CSF) it is possible to make a definitive differentiation between the two brain diseases.

Scientists at the University of Pennsylvania (Philadelphia, PA, USA) studied 142 neuropathologically diagnosed neurodegenerative dementia patients, including 71 with AD, 29 with FTLD, three with amyotrophic lateral sclerosis, seven with dementia with Lewy bodies, and 32 with mixed diagnosis. For 136 patients there was enzyme linked immunosorbent assay (ELISA) CSF data for comparison to 43 controls and for 110 patients there was Luminex CSF data for comparison with 46 controls. Amyloid beta (Aβ42), total, and phosphorylated tau181 were measured.

The investigators determined that values from the two platforms could effectively be transformed into equivalent units, and these values accurately distinguished AD from FTLD. A cutoff of 0.34 for the t-tau: Aβ1-42 ratio had 90% to 100% sensitivity and 91% to 96.7% specificity to differentiate FTLD cases, respectively. Clinical and neuropathological diagnoses showed an 81.3% overall agreement. ELISA and Luminex showed high sensitivity and specificity to classify AD subjects against FTLD subjects and controls and moderate sensitivity and specificity for classifying FTLD subjects against controls. The ELISA platform revealed 69.4% and the Luminex (Austin, TX, USA) platform 96.4% of the cases with mixed neuropathological diagnoses including a diagnosis AD (which was 24.8% of the sample), were classified as AD. Probabilities obtained by models based on clinical and neuropathological diagnoses differed and underestimated the true diagnostic accuracy.

John Q. Trojanowski, MD, PhD, professor of Pathology and Laboratory Medicine and co-director of the Center for Neurodegenerative Disease Research, said, "With the emergence of disease-modifying treatments for AD and other neurodegenerative diseases, it will be of utmost importance to accurately identify the underlying neuropathology in patients." Murray Grossman, MD, professor of Neurology, and senior author of the study added, "We need to develop better CSF diagnostic panels for the early diagnosis of neurodegenerative dementias, including those due to mixed neurodegenerative disease pathologies that commonly co-occur with Alzheimer's." The studies were presented at the American Academy of Neurology's 64th Annual Meeting, held April 21 to April 28, 2012, in New Orleans (LA, USA).

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