Cited by 182Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsCerebrospinal fluid and hydrocephalus

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CSF biomarkers cutoffs: the importance of coincident neuropathological diseases

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Toledo, Jon B., Brettschneider, Johannes, Grossman, Murray, Arnold, Steven E., Hu, William T., Xie, Sharon X., Lee, Virginia M.-Y., Shaw, Leslie M., Trojanowski, John Q.·2012·Acta Neuropathologica

DOI 10.1007/s00401-012-0983-7PMC PMC3551449

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Abstract

The effects of applying clinical versus neuropathological diagnosis and the inclusion of cases with coincident neuropathological diagnoses have not been assessed specifically when studying cerebrospinal fluid (CSF) biomarker classification cutoffs for patients with neurodegenerative diseases that cause dementia. Thus, 142 neuropathologically diagnosed neurodegenerative dementia patients [71 Alzheimer's disease (AD), 29 frontotemporal lobar degeneration (FTLD), 3 amyotrophic lateral sclerosis, 7 dementia with Lewy bodies, 32 of which cases also had coincident diagnoses] were studied. 96 % had enzyme-linked immunosorbant assay (ELISA) CSF data and 77 % had Luminex CSF data, with 43 and 46 controls for comparison, respectively. Aβ(42), total, and phosphorylated tau(181) were measured. Clinical and neuropathological diagnoses showed an 81.4 % overall agreement. Both assays showed high sensitivity and specificity to classify AD subjects against FTLD subjects and controls, and moderate sensitivity and specificity for classifying FTLD subjects against controls. However, among the cases with neuropathological diagnoses of AD plus another pathology (26.8 % of the sample), 69.4 % (ELISA) and 96.4 % (Luminex) were classified as AD according to their biomarker profiles. Use of clinical diagnosis instead of neuropathological diagnosis led to a 14-17 % underestimation of the biomarker accuracy. These results show that while CSF Aβ and tau assays are useful for diagnosis of AD and neurodegenerative diseases even at MCI stages, CSF diagnostic analyte panels that establish a positive diagnosis of Lewy body disease and FTLD are also needed, and must be established based on neuropathological rather than clinical diagnoses.

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Authors: Toledo, J. B., Brettschneider, J., Grossman, M., Arnold, S. E., Hu, W. T., Xie, S. X., Lee, V. M.-Y., Shaw, L. M., & Trojanowski, J. Q.
Affiliations: University of Pennsylvania (US)
Emory University (US)
Corresponding author: Trojanowski, John Q.
ORCID: Toledo, Jon B.
Grossman, Murray
Arnold, Steven E.
Hu, William T.
Xie, Sharon X.
Lee, Virginia M.-Y.
Shaw, Leslie M.
Trojanowski, John Q.
Venue: Acta Neuropathologica
Publisher: Springer Science and Business Media LLC
Published: 2012-04-22
Volume: 124
Issue: 1
Pages: 23-35
ISSN: 0001-6322 (ISSN-L)
1432-0533
DOI: 10.1007/s00401-012-0983-7
PMC: PMC3551449
OpenAlex: W2022371215
Cited by: 182
References: 71
Citations by year: 2026: 3 · 2025: 7 · 2024: 8 · 2023: 3 · 2022: 14 · 2021: 7 · 2020: 9 · 2019: 15 · 2018: 19 · 2017: 17 · 2016: 11 · 2015: 27 · 2014: 15 · 2013: 22 · 2012: 5
FWCI: 15.76
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Acta Neuropathologica (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: University of Pennsylvania
National Institutes of Health
National Institute on Aging (AG15116, AG033101, P30AG010124, R01AG015116, P01AG017586, AG17586, AG-10124, K08AG033101)
National Institute of Neurological Disorders and Stroke (P01NS044233, NS053488, NS-44266, P50NS053488, R01NS044266)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Health Sciences › Medicine › Clinical Neurology › Cerebrospinal fluid and hydrocephalus
Keywords: cerebrospinal fluid biomarkers, Alzheimer's disease, frontotemporal lobar degeneration, dementia with Lewy bodies, amyotrophic lateral sclerosis, amyloid-beta 42, phosphorylated tau 181, diagnostic accuracy, neurodegenerative dementia, mild cognitive impairment, biomarker cut-off values
MeSH terms: Aged, Aged, 80 and over, Alzheimer Disease, Amyotrophic Lateral Sclerosis, Analysis of Variance, Enzyme-Linked Immunosorbent Assay, Female, Humans, Male, Middle Aged, Peptide Fragments, Psychiatric Status Rating Scales, Sensitivity and Specificity, Biomarkers, Amyloid beta-Peptides, tau Proteins, Area Under Curve, Frontotemporal Lobar Degeneration, Frontotemporal Dementia

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