Neurochemical biomarkers in the differential diagnosis of movement disorders

Recently, Mollenhauer and Trenkwalder, 1 in an extensive and critical review of CSF biomarkers in the differential diagnosis of movement disorders, stated that differences of total tau (TT) between PD and PDD are only marginal, but elevated in both dementia with Lewy bodies (DLB) and multiple system atrophy (MSA), whereas CSF Ab-42 in PD (no dementia) is normal or only slightly decreased, and regularly decreased in both DLB and MSA. These data can be confirmed by personal studies in a small cohort of patients, in whom both CSF Ab-42 and total tau protein were measured. The sample included (1) 10 patients who fulfilled the UK Parkinson Brain Bank criteria for clinically definite PD 2 (8 males, 2 females aged 46–76, mean 63.2 6 7.8 years), all Hoehn & Yahr stages III or IV, none being demented; (2) 12 patients (6 males, 8 females, aged 71–88, mean 77.9 6 8.3 years) with the clinical diagnosis of secondary parkinsonism related to vascular encephalopathy or suspected vascular parkinsonism 3 ; (3) 3 patients with atypical parkinsonism fulfilling the diagnostic criteria of MSA-P 4 (2 males, 1 female aged 53– 70, mean 61.3 6 7.1 years); (4) 2 males (age 63 and 84, mean 73.5 years) fulfilling the criteria of probable DLB. 5 The control group consisted of 17 age-matched patients without neurologic or psychiatric disorders (mean age 60.7 6 1.5 years), while 27 patients (mean age 68.7 6 2.1 years) were diagnosed probable Alzheimer disease (AD) according to the NINCDSADRDA criteria. 6 Examination of lumbar CS was performed using ELISA methods for Ab-42 and TT immunoreactivity (Innogenetics, Belgium)—for methods see Ref. 7. The results are summarized in Table 1. In both PD patients without dementia and in those with vascular pseudoparkinsonism, both CSF Ab-42 and TT levels were only insignificantly increased, but significantly differed from those in AD. The mild increase of CSF Ab-42 is at variance to the findings by others (see 1), as were our findings in a small group of patients with atypical parkinsonism (MSA-P), indicating increased CSF Ab-42 without considerable changes in TT immunoreactivity. These levels considerably differed from the 2 demented patients with DLB, where Ab-42 was mildly decreased and TT-IR was significantly—around twofold—increased versus controls and PD patients (P < 0.01). This suggested additional AD-related changes, although CSF levels of both Ab-42 and TT differed significantly from those in AD. The latter findings are in accordance with those by others, who either reported decreased Ab-42 and normal tau levels in DLB or normal Ab-42 and decreased phosphorylated tau (see 1). In conclusion, considering the variability in Ab-42 and TT levels in CSF in various types of movement disorders, further prospective clinico-pathological correlative studies using modern proteomics are needed to further elucidate the validity and to increase the sensitivity and specificity of CSF markers in movement disorders.