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The clinical diagnosis of Parkinson's disease (PD) and Dementia with Lewy bodies (DLB) is challenging due to highly variable clinical presentation and clinical and pathological overlap with other neurodegenerative diseases. Since cerebrospinal fluid (CSF) mirrors the pathological changes taking place in the brain, it represents a promising source of biomarkers. With respect to classical AD biomarkers, low CSF Aβ 42 levels have shown a robust prognostic value in terms of development of cognitive impairment in PD and DLB. In the differential diagnosis between AD and DLB, a potential role of t-tau, p-tau and Aβ 42 /Aβ 38 ratio has been demonstrated. Regarding CSF α-synuclein (α-syn) species, lower levels of total α-synuclein (t-α-syn) and higher concentration of oligomeric-α-synuclein (o-α-syn) and phosphorylated α-synuclein (p-α-syn) have been observed in PD. Furthermore, the detection of "pro-aggregating" α-synuclein has enabled the discrimination of patients affected by synucleinopathies with high sensitivity and specificity. New promising biomarkers are emerging: GCase activity (reduced in PD and DLB patients vs. controls), CSF/serum albumin ratio (increased in PD and DLB), fatty-acid-binding protein (increased in AD and DLB vs. PD), visinin-like protein-1 (increased in AD vs. DLB) and monoamines (useful in differential diagnosis among PD and DLB). These encouraging results need to be confirmed by future studies., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The cerebrospinal fluid (CSF) signature of Alzheimer's disease (AD) includes abnormal levels of amyloid-β 1-42 (Aβ42), total tau (t-Tau) and phosphorylated tau (p-Tau). Several studies have reported that the CSF Aβ42/Aβ40 ratio could outperform CSF Aβ42 as a more accurate marker of brain amyloidosis, since it normalizes the CSF Aβ42 levels according to the total production of Aβ in the brain. In the present study, we wanted to assess the diagnostic utility of adding the Aβ42/Aβ40 ratio within the core AD CSF biomarkers for the classification of patients, according to NIA-AA criteria and Erlangen score. We consecutively recruited 168 patients (62 with AD and 106 with other neurological diseases) who referred to our Memory Clinic for diagnostic work- up from 2003 to 2016. The use of CSF Aβ42/Aβ40 ratio increased the percentage of correctly diagnosed AD patients from 72.0% to 82.8%. The high gain in sensitivity (from 75.8% to 85.5%) was obtained in face of loss of specificity (from 95.3% to 82.5%). Our study showed that the use of CSF Aβ42/Aβ40 could significantly improve the routine diagnostic work up of AD., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The variability of Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers (Aβ42, t-Tau and p-Tau) undermines their full-fledged introduction into routine diagnostics and clinical trials. The introduction of automatic systems can improve the diagnostic performance promoting standardization and reducing the impact of preanalytical and analytical factors. Here we assessed the diagnostic performance of a fully automated chemiluminescent enzyme assay (LUMIPULSE) and compared it with that obtained by using the classical manual enzyme-linked immunosorbent assays (ELISAs). Patients were clinically diagnosed as AD (n = 42) and non-AD (n = 38). Clinical diagnosis was confirmed at follow-up. LUMIPULSE Aβ42 was reduced in AD (969.4 ± 329.6 pg/mL vs. 1625.9 ± 745.9 pg/mL, p <0.001), whereas LUMIPULSE t-Tau was increased in AD (768.2 ± 281.0 pg/mL vs. 337.5 ± 159.1 pg/mL, p < 0.001) compared to non-AD patients. Both LUMIPULSE Aβ42 (AUC = 0.78, spec. = 0.74, sens. = 0.76) and t-Tau (AUC = 0.94, spec. = 0.93, sens. = 0.87) showed good accuracy in distinguish AD from non-AD and a high correlation with the manual ELISAs (r = 0.87, p < 0.001 and r = 0.92, p < 0.001, respectively). LUMIPULSE improves clinical accuracy in AD diagnosis, promoting the use of standardized values for CSF biomarkers with a good correlation with classical manual assays., (Copyright © 2019 Elsevier B.V. All rights reserved.)