Journal
JOURNAL OF ALZHEIMERS DISEASE
Volume 27, Issue 2, Pages 377-384Publisher
IOS PRESS
DOI: 10.3233/JAD-2011-110482
Keywords
Alzheimer's disease; amyloid-beta; cerebrospinal fluid; dementia with Lewy bodies; diagnosis; MHPG; neurotransmitter metabolites; tau
Categories
Funding
- Stichting Internationaal Parkinson Fonds
- Van Alkemade-Keuls Fonds
- Netherlands Heart Foundation
- DEVON foundation
- ZonMW VIDI [91746331, 91776352]
- Dutch Brain Foundation
- Centre for Translational Molecular Medicine
- AADC research trust
- American Alzheimer Association
- ADDF
- Jansen-Cilag
- Novartis
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Differentiating dementia with Lewy bodies (DLB) from Alzheimer's Disease (AD) can be difficult because of the substantial overlap in clinical features. Since deficits in serotonergic and dopaminergic pathways seem more pronounced in DLB patients, we investigated whether cerebrospinal fluid (CSF) analysis of neurotransmitter metabolites, in addition to brain-specific proteins, may improve the differentiation between DLB and AD. We retrospectively compared CSF concentrations of the neurotransmitter metabolites homovanillic acid (HVA), 5-hydroxyindolacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) and the brain-specific proteins total tau (t-tau), phosphorylated tau protein (p-tau), and amyloid-beta(42) (A beta(42)) in 45 patients with AD (mean age 71.6 years; 34 (76%) men; 44 probable AD, 1 definite) and 23 patients with DLB (mean age 71.6 years; 18 (78%) men; 6 possible DLB, 16 probable, 1 definite). The concentrations of all neurotransmitter metabolites, as well as those for t-tau and p-tau protein, were significantly lower in DLB compared to AD, irrespective of the diagnostic certainty (i.e., possible or probable). The currently used combination of A beta(42), p-tau, and t-tau yielded a sensitivity of 92.9% and a specificity of 90%. The addition of MHPG resulted in an increased sensitivity of 97.6% and a specificity of 95% for the discrimination between DLB and AD. In conclusion, the combination of MHPG and the brain specific proteins t-tau, p-tau, and A beta(42) in CSF were associated with the clinical diagnosis of DLB and discriminated between AD and DLB with high diagnostic accuracy, suggesting this combination as a potential biomarker for DLB.
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