CSF Tau, Aβ42, and MHPG Differentiate Dementia with Lewy Bodies from Alzheimer's Disease

Abstract

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-β42 (Aβ42) 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 Aβ42, 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 Aβ42 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.

Cerebrospinal Fluid α-Synuclein In the Differential Diagnosis of Parkinsonian Syndromes

“…By contrast, other studies fail to demonstrate any differentiating capability of α-synuclein CSF levels among parkinsonian syndromes [22]. The absolute concentration values measured in the present study correspond well with other recent reports [41] but are much lower (at least by a factor of 3) than those reported by other groups [39][40]42] -that is, we found a mean of 528 ± 312 pg/ml in the disease control groups and 269 ± 352 pg/ml in the PD group. Compared with other studies that report concentrations measured in ng/ml values [22,43], the concentration discrepancy is even more pronounced.…”

Using Cerebrospinal Fluid Marker Profiles in Clinical Diagnosis of Dementia with Lewy Bodies, Parkinson's Disease, and Alzheimer's Disease

“…A␤ 42 levels were reported to be decreased in AD compared to healthy controls and DLB [14]. At the same time, A␤ 42 is supposed to be very useful for differential diagnosis in combination with t-tau and p-tau with a sensitivity of 93% and a specificity of 95% when all three biomarkers were used [15]. We also conclude that a combined detection of increased tau and a pronounced decrease in A␤ 42 helps to distinguish DLB from other dementias, especially AD and PD, which was unfortunately not true for mild stages of DLB.…”

Interaction between pathogenic proteins in neurodegenerative disorders

“…The intercellular transfer of cytosolic protein aggregates may also occur through nanotubes, exosomes or microvesicles [244]. Like other pathogenic proteins, Ab can be taken up, modified and secreted by cells in vitro [118,266], and-together with tau-it is also present in the CSF [267][268][269]. At the current state of knowledge, the exact involvement in the pathophysiology of prion disease and the NDDs is not fully understood and deserves further investigation to elucidate the possible overlaps between these disorders.…”