Alzheimer's disease biomarker‐guided diagnostic workflow using the added value of six combined cerebrospinal fluid candidates: Aβ1–42, total‐tau, phosphorylated‐tau, NFL, neurogranin, and YKL‐40
Abstract
Introduction: The diagnostic and classificatory performances of all combinations of three core (amyloid β peptide [i.e., Aβ 1–42], total tau [t‐tau], and phosphorylated tau) and three novel (neurofilament light chain protein, neurogranin, and YKL‐40) cerebrospinal fluid biomarkers of neurodegeneration were compared among individuals with mild cognitive impairment (n = 41), Alzheimer's disease dementia (ADD; n = 35), frontotemporal dementia (FTD; n = 9), and cognitively healthy controls (HC; n = 21), using 10‐fold cross‐validation. Methods: The combinations ranking in the top 10 according to diagnostic accuracy in differentiating between distinct diagnostic categories were identified. Results: The single biomarkers or biomarker combinations generating the best area under the receiver operating characteristics (AUROCs) were the following: the combination [amyloid β peptide + phosphorylated tau + neurofilament light chain] for distinguishing between ADD patients and HC (AUROC = 0.86), t‐tau for distinguishing between ADD and FTD patients (AUROC = 0.82), and t‐tau for distinguishing between FTD patients and HC (AUROC = 0.78). Conclusions: Novel and established cerebrospinal fluid markers perform with at least fair accuracy in the discrimination between ADD and FTD. The classification of mild cognitive impairment individuals was poor.
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Levels of various additional proteins have been suggested as endophenotypes for AD, the clinical and biological relevance of which remain to be elucidated.
“along with levels of various additional proteins, the clinical and biological relevance of which remain to be elucidated [216–218].”
From Genetic architecture of Alzheimer's disease (2020) · cites this paper as [216]
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“The group clinically defined as MCI included 41 participants [30].”
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- Authors
- Hampel, H., Toschi, N., Baldacci, F., Zetterberg, H., Blennow, K., Kilimann, I., Teipel, S. J., Cavedo, E., Melo dos Santos, A., Epelbaum, S., Lamari, F., Genthon, R., Dubois, B., Floris, R., Garaci, F., Lista, S., & (APMI), A. P. M. I.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- University of Rome Tor Vergata (IT)
- University of Pisa (IT)
- Sahlgrenska University Hospital (SE)
- University of Rostock (DE)
- Sorbonne Université, AP‐HP, GRC n° 21 Alzheimer Precision Medicine (APM), Hôpital de la Pitié‐Salpêtrière Paris France
- Assistance Publique – Hôpitaux de Paris (FR)
- Sorbonne Université (FR)
- ORCID
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2018-01-09
- Volume
- 14
- Issue
- 4
- Pages
- 492-501
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- OpenAlex
- W2782731988
- Cited by
- 129
- References
- 8
- Citations by year
- 2026: 6 · 2025: 13 · 2024: 9 · 2023: 6 · 2022: 12 · 2021: 17 · 2020: 31 · 2019: 24 · 2018: 11
- FWCI
- 16.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Alzheimer s & Dementia (publishedVersion)
- PubMed (publishedVersion)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
- Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion)
- DZNE Pub (submittedVersion)
- Funders
- Pfizer
- AXA Research Fund
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
- Keywords
- Alzheimer's disease, frontotemporal dementia
- MeSH terms
- Chitinase-3-Like Protein 1, Aged, Alzheimer Disease, Cross-Sectional Studies, Diagnosis, Differential, Female, Humans, Male, Middle Aged, Nuclear Proteins, Peptide Fragments, Retrospective Studies, ROC Curve, Biomarkers, Amyloid beta-Peptides, RNA-Binding Proteins, tau Proteins, Neurofilament Proteins, Area Under Curve, Frontotemporal Dementia, Cognitive Dysfunction
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