Objective: To determine how amyloid ␤ 42 (A␤42), total tau (t-tau), and phosphorylated tau (p-tau) levels in CSF behave in a large cohort of patients with different types of dementia. Methods:Baseline CSF was collected from 512 patients with Alzheimer disease (AD) and 272 patients with other types of dementia (OD), 135 patients with a psychiatric disorder (PSY), and 275 patients with subjective memory complaints (SMC). A␤42, t-tau, and p-tau (at amino acid 181) were measured in CSF by ELISA. Autopsy was obtained in a subgroup of 17 patients.Results: A correct classification of patients with AD (92%) and patients with OD (66%) was accomplished when CSF A␤42 and p-tau were combined. Patients with progressive supranuclear palsy had normal CSF biomarker values in 90%. Patients with Creutzfeldt-Jakob disease demonstrated an extremely high CSF t-tau at a relatively normal CSF p-tau. CSF AD biomarker profile was seen in 47% of patients with dementia with Lewy bodies (DLB), 38% in corticobasal degeneration (CBD), and almost 30% in frontotemporal lobar degeneration (FTLD) and vascular dementia (VaD). PSY and SMC patients had normal CSF biomarkers in 91% and 88%. Older patients are more likely to have a CSF AD profile. Concordance between clinical and neuropathologic diagnosis was 85%. CSF markers reflected neuropathology in 94%.Conclusion: CSF A␤42, t-tau, and p-tau are useful in differential dementia diagnosis. However, in DLB, FTLD, VaD, and CBD, a substantial group exhibit a CSF AD biomarker profile, which requires more autopsy confirmation in the future. Neurology ® 2012;78:47-54 GLOSSARY A␤42 ϭ amyloid ␤ 42; AD ϭ Alzheimer disease; BNE ϭ BrainNet Europe; CBD ϭ corticobasal degeneration; CI ϭ confidence interval; CJD ϭ Creutzfeldt-Jakob disease; DLB ϭ dementia with Lewy bodies; FTLD ϭ frontotemporal lobar degeneration; IQR ϭ interquartile range; MMSE ϭ Mini-Mental State Examination; NINDS ϭ National Institute of Neurological Disorders and Stroke; OD ϭ other types of dementia; OR ϭ odds ratio; p-tau ϭ phosphorylated tau; PSP ϭ progressive supranuclear palsy; PSY ϭ psychiatric disorder; SMC ϭ subjective memory complaints; t-tau ϭ total tau; VaD ϭ vascular dementia.

Background: Immunoreactivity for several chemokines and for their related receptors has been demonstrated in resident cells of the central nervous system, and the up-regulation of some of them is associated with pathological changes found in Alzheimer disease (AD). Objective: To determine interferon-␥-inducible protein 10 (IP-10), monocyte chemotactic protein 1 (MCP-1), and interleukin 8 (IL-8) levels in cerebrospinal fluid (CSF) from subjects with amnestic mild cognitive impairment (MCI) and patients with AD as compared with agematched controls. Patients: Thirty-eight subjects with amnestic MCI, 36 patients with AD, and 41 age-matched subjects with noninflammatory affections of the nervous system. Design: Evaluation of CSF chemokine production at time of diagnosis of MCI and AD; correlation with clinical and personal data. Longitudinal evaluation of subjects with MCI until conversion to AD. Results: Cerebrospinal fluid IP-10 concentration was significantly increased in patients with MCI and mild AD but not in patients with severe AD (Mini-Mental State Examination score Ͻ15), whereas MCP-1 and IL-8 levels were increased in patients with MCI and all patients with AD. A significant positive correlation between Mini-Mental State Examination score and CSF IP-10 or MCP-1 concentration was observed in patients with AD. No correlation between IP-10 levels and age was found, whereas MCP-1 and IL-8 levels correlated positively with age. Out of 38 subjects with MCI, 19 developed AD within a 1-to 3-year follow-up. Conclusions: The presence of inflammatory molecules is likely to be a very early event in AD pathogenesis, even preceding the clinical onset of the disease, as demonstrated by subjects with MCI who developed AD over time. Interferon-␥-inducible protein 10 is specifically increased in MCI and seems to decrease with the progression of AD, whereas MCP-1 and IL-8 are up-regulated also in late stages of the disease, suggesting a role in phases in which neurodegeneration is prevalent.

Background: Reported concentrations of amyloid ␤ (1-42) (A␤42) and tau in cerebrospinal fluid (CSF) differ among reports. We investigated the effects of storage temperature, repeated freeze/thaw cycles, and centrifugation on the concentrations of A␤42 and tau in CSF. Methods: Stability of samples stored at ؊80°C was determined by use of an accelerated stability testing protocol according to the Arrhenius equation. A␤42 and tau concentrations were measured in CSF samples stored at 4, 18, 37, and ؊80°C. Relative CSF concentrations (%) of the biomarkers after one freeze/thaw cycle were compared with those after two, three, four, five, and six freeze/thaw cycles. In addition, relative A␤42 and tau concentrations in samples not centrifuged were compared with samples centrifuged after 1, 4, 48, and 72 h. Results: A␤42 and tau concentrations were stable in CSF when stored for a long period at ؊80°C. CSF A␤42 decreased by 20% during the first 2 days at 4, 18, and 37°C compared with ؊80°C. CSF tau decreased after storage for 12 days at 37°C. After three freeze/thaw cycles, CSF A␤42 decreased 20%. CSF tau was stable during six freeze/thaw cycles. Centrifugation did not influence the biomarker concentrations.

The combination of CSF Abeta42 and CSF Ptau-181 may help in differentiating EAD from FTLD.

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Levels of CSF beta-amyloid(1-42) and tau but not phosphorylated tau at threonine 181 increased over time in this memory clinic patient cohort with comparable change in all diagnostic groups. The cross-sectional difference between diagnostic groups, however, exceeded by far the longitudinal changes within individuals, suggesting that these biomarkers are not sensitive as markers of disease progression.

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