Accuracy of a Panel of 5 Cerebrospinal Fluid Biomarkers in the Differential Diagnosis of Patients With Dementia and/or Parkinsonian Disorders
Abstract
OBJECTIVE: To assess the ability of 5 cerebrospinal fluid(CSF) biomarkers to differentiate between common dementia and parkinsonian disorders. DESIGN: A cross-sectional, clinic-based study. PARTICIPANTS: Cerebrospinal fluid samples (N=453) were obtained from healthy individuals serving as controls and from patients with Parkinson disease (PD), PD with dementia(PDD), dementia with Lewy bodies (DLB), Alzheimer disease (AD), progressive supranuclear palsy(PSP), multiple system atrophy (MSA), or corticobasal degeneration (CBD). SETTING: Neurology and memory disorder clinics. MAIN OUTCOME MEASURES: Cerebrospinal fluid biomarker levels in relation to clinical diagnosis. RESULTS: Cerebrospinal fluid levels of -synuclein were decreased in patients with PD, PDD, DLB, and MSA but increased in patients with AD. Cerebrospinal fluid levels of α-amyloid 1-42 were decreased in DLB and even further decreased in AD. Cerebrospinal fluid levels of total tau and hyperphosphorylated tau were increased in AD. Multivariate analysis revealed that these biomarkers could differentiate AD from DLB and PDD with an area under the curve of 0.90, with -synuclein and total tau contributing most to the model. Cerebrospinal fluid levels of neurofilament light chain were substantially increased in atypical parkinsonian disorders (ie, PSP, MSA,and CBD), and multivariate analysis revealed that the level of neurofilament light chain alone could differentiate PD from atypical parkinsonian disorders, with an area under the curve of 0.93. CONCLUSIONS: Ascertainment of the -synuclein level in CSF somewhat improves the differential diagnosis of AD vs DLB and PDD when combined with established AD biomarkers.The level of neurofilament light chain alone may differentiate PD from atypical parkinsonian disorders.
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CSF tau levels are not increased in non-AD tauopathies.
“CSF tau levels are not increased in non-AD tauopathies57–60, suggesting that extracellular tau is not a primary target in these conditions.”
From Tau-targeting therapies for Alzheimer disease (2018) · cites this paper as [57]
Extracellular tau is not a primary target in non-AD tauopathies.
“CSF tau levels are not increased in non-AD tauopathies57–60, suggesting that extracellular tau is not a primary target in these conditions.”
From Tau-targeting therapies for Alzheimer disease (2018) · cites this paper as [57]
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Kruse, N., Persson, S., Alcolea, D., Bahl, J. M. C., Baldeiras, I., Capello, E., Chiasserini, D., Bocchio Chiavetto, L., Emersic, A., Engelborghs, S., et al. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2015.05.003 · Cited by 38 · see citing works
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Progress Update: Fluid and Imaging Biomarkers in Alzheimer’s Disease
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Diagnosing progressive supranuclear palsy: Role of biological and neuroimaging markers
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- Authors
- Hall, S., Öhrfelt, A., Constantinescu, R., Andreasson, U., Surova, Y., Bostrom, F., Nilsson, C., Widner, H., Decraemer, H., Nägga, K., Minthon, L., Londos, E., Vanmechelen, E., Holmberg, B., Zetterberg, H., Blennow, K., & Hansson, O.
- Affiliations
- Lund University (SE)
- ORCID
- Venue
- Archives of Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2012-11-01
- Volume
- 69
- Issue
- 11
- Pages
- 1445
- ISSN
- 0003-9942 (ISSN-L)
- OpenAlex
- W2160719857
- Cited by
- 473
- References
- 48
- Citations by year
- 2026: 9 · 2025: 22 · 2024: 31 · 2023: 24 · 2022: 43 · 2021: 41 · 2020: 34 · 2019: 49 · 2018: 44 · 2017: 37 · 2016: 38 · 2015: 26 · 2014: 36 · 2013: 32 · 2012: 5
- FWCI
- 22.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of Neurology (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- cerebrospinal fluid biomarkers, differential diagnosis, dementia, parkinsonism, Parkinson's disease, Parkinson's disease dementia, dementia with Lewy bodies, Alzheimer's disease, progressive supranuclear palsy, multiple system atrophy, corticobasal degeneration, alpha-synuclein, tau protein, phosphorylated tau, neurofilament light chain, atypical parkinsonism
- MeSH terms
- Aged, Aged, 80 and over, Cross-Sectional Studies, Dementia, Diagnosis, Differential, Enzyme-Linked Immunosorbent Assay, Female, Hemoglobins, Humans, Male, Middle Aged, Neuropsychological Tests, Parkinson Disease, Psychiatric Status Rating Scales, Severity of Illness Index, Supranuclear Palsy, Progressive, Biomarkers, Amyloid beta-Peptides, tau Proteins, Statistics, Nonparametric, Multiple System Atrophy, Neurodegenerative Diseases, alpha-Synuclein
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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