A panel of nine cerebrospinal fluid biomarkers may identify patients with atypical parkinsonian syndromes.

Patients presenting with parkinsonian syndromes share many clinical features, which can make diagnosis difficult. This is important as atypical parkinsonian syndromes (APSs) such as progressive supranuclear palsy (PSP), multiple system atrophy (MSA) and corticobasal syndrome (CBS) carry a poor prognosis, compared with patients with Parkinson's disease (PD). In addition, there is overlap between APS and dementia diseases, such as Alzheimer's disease (AD) and frontotemporal dementia (FTD). To use a panel of cerebrospinal fluid (CSF) biomarkers to differentiate patients with APS from PD and dementia. A prospective cohort of 160 patients and 30 control participants were recruited from a single specialist centre. Patients were clinically diagnosed according to current consensus criteria. CSF samples were obtained from patients with clinical diagnoses of PD (n=31), PSP (n=33), CBS (n=14), MSA (n=31), AD (n=26) and FTD (n=16). Healthy, elderly participants (n=30) were included as controls. Total τ (t-τ), phosphorylated τ (p-τ), β-amyloid 1-42 (Aβ42), neurofilament light chain (NFL), α-synuclein (α-syn), amyloid precursor protein soluble metabolites α and β (soluble amyloid precursor protein (sAPP)α, sAPPβ) and two neuroinflammatory markers (monocyte chemoattractant protein-1 and YKL-40) were measured in CSF. A reverse stepwise regression analysis and the false discovery rate procedure were used. CSF NFL (p<0.001), sAPPα (p<0.001) and a-syn (p=0.003) independently predicted diagnosis of PD versus APS. Together, these nine biomarkers could differentiate patients with PD from APS with an area under the curve of 0.95 and subtypes of APS from one another. There was good discriminatory power between parkinsonian groups, dementia disorders and healthy controls. A panel of nine CSF biomarkers was able to differentiate APS from patients with PD and dementia. This may have important clinical utility in improving diagnostic accuracy, allowing better prognostication and earlier access to potential disease-modifying therapies.

Magdalinou NK ，Paterson RW ，Schott JM ，Fox NC ，Mummery C ，Blennow K ，Bhatia K ，Morris HR ，Giunti P ，Warner TT ，de Silva R ，Lees AJ ，Zetterberg H ... -  《-》

Accuracy of a panel of 5 cerebrospinal fluid biomarkers in the differential diagnosis of patients with dementia and/or parkinsonian disorders.

Hall S ，Öhrfelt A ，Constantinescu R ，Andreasson U ，Surova Y ，Bostrom F ，Nilsson C ，Håkan W ，Decraemer H ，Någga K ，Minthon L ，Londos E ，Vanmechelen E ，Holmberg B ，Zetterberg H ，Blennow K ，Hansson O ... -  《-》

CSF biomarkers distinguish idiopathic normal pressure hydrocephalus from its mimics.

To examine the differential diagnostic significance of cerebrospinal fluid (CSF) biomarkers reflecting Alzheimer's disease-related amyloid β (Aβ) production and aggregation, cortical neuronal damage, tau pathology, damage to long myelinated axons and astrocyte activation, which hypothetically separates patients with idiopathic normal pressure hydrocephalus (iNPH) from patients with other neurodegenerative disorders. The study included lumbar CSF samples from 82 patients with iNPH, 75 with vascular dementia, 70 with Parkinson's disease, 34 with multiple system atrophy, 34 with progressive supranuclear palsy, 15 with corticobasal degeneration, 50 with Alzheimer's disease, 19 with frontotemporal lobar degeneration and 54 healthy individuals (HIs). We analysed soluble amyloid precursor protein alpha (sAPPα) and beta (sAPPβ), Aβ species (Aβ38, Aβ40 and Aβ42), total tau (T-tau), phosphorylated tau, neurofilament light and monocyte chemoattractant protein 1 (MCP-1). Patients with iNPH had lower concentrations of tau and APP-derived proteins in combination with elevated MCP-1 compared with HI and the non-iNPH disorders. T-tau, Aβ40 and MCP-1 together yielded an area under the curve of 0.86, differentiating iNPH from the other disorders. A prediction algorithm consisting of T-tau, Aβ40 and MCP-1 was designed as a diagnostic tool using CSF biomarkers. The combination of the CSF biomarkers T-tau, Aβ40 and MCP-1 separates iNPH from cognitive and movement disorders with good diagnostic sensitivity and specificity. This may have important implications for diagnosis and clinical research on disease mechanisms for iNPH.

Jeppsson A ，Wikkelsö C ，Blennow K ，Zetterberg H ，Constantinescu R ，Remes AM ，Herukka SK ，Rauramaa T ，Nagga K ，Leinonen V ，Tullberg M ... -  《-》

Diagnosis Across the Spectrum of Progressive Supranuclear Palsy and Corticobasal Syndrome.

Jabbari E ，Holland N ，Chelban V ，Jones PS ，Lamb R ，Rawlinson C ，Guo T ，Costantini AA ，Tan MMX ，Heslegrave AJ ，Roncaroli F ，Klein JC ，Ansorge O ，Allinson KSJ ，Jaunmuktane Z ，Holton JL ，Revesz T ，Warner TT ，Lees AJ ，Zetterberg H ，Russell LL ，Bocchetta M ，Rohrer JD ，Williams NM ，Grosset DG ，Burn DJ ，Pavese N ，Gerhard A ，Kobylecki C ，Leigh PN ，Church A ，Hu MTM ，Woodside J ，Houlden H ，Rowe JB ，Morris HR ... -  《-》

CSF biomarkers β-amyloid, tau proteins and a-synuclein in the differential diagnosis of Parkinson-plus syndromes.

Differential diagnosis of Parkinson-plus patients (PSP, CBD, MSA) and Parkinson's disease (PD) patients is often not straightforward, particularly in atypical cases or at the initial stages of the diseases. Classic CSF biomarkers (amyloid-beta - Aβ42, tau protein - τT and phosphorylated tau protein - τP-181) are established biomarkers in the diagnosis of Alzheimer's disease (AD). CSF a-synuclein (α-syn) has emerged as a promising biomarker in patients with Parkinsonism. The aim of this study was to analyze the CSF biochemical profile of patients with Parkinsonism. We analyzed the CSF biomarker profile (Aβ42, τT, τP-181, α-syn) and all relevant ratios in 68 patients with Parkinsonism (19 PSP, 15 MSA, 17 CBD, 17 PD) and 18 controls, diagnosed by latest established diagnostic criteria. CBD patients exhibited elevated τT and decreased Aβ42 compared to the other groups. Five CBD, one PSP patient and one control had a typical AD CSF profile. After exclusion of these patients, the τT/Aβ42 ratio was significantly elevated in MSA patients compared to PD patients and provided excellent specificity and adequate sensitivity in their differential diagnosis. CSF biochemical profile analysis is important in distinguishing AD patients with a CBS phenotype from non-AD CBS patients. The τT/Aβ42 ratio is useful in the differential diagnosis of MSA from PD.

Constantinides VC ，Paraskevas GP ，Emmanouilidou E ，Petropoulou O ，Bougea A ，Vekrellis K ，Evdokimidis I ，Stamboulis E ，Kapaki E ... -  《-》