Fluid biomarkers in Alzheimer's disease
Abstract
Alzheimer's disease (AD) characterization has progressed from being indexed using clinical symptomatology followed by neuropathological examination at autopsy to in vivo signatures using cerebrospinal fluid (CSF) biomarkers and positron emission tomography. The core AD biomarkers reflect amyloid-β plaques (A), tau pathology (T) and neurodegeneration (N), following the ATN schedule, and are now being introduced into clinical routine practice. This is an important development, as disease-modifying treatments are now emerging. Further, there are now reproducible data on CSF biomarkers which reflect synaptic pathology, neuroinflammation and common co-pathologies. In addition, the development of ultrasensitive techniques has enabled the core CSF biomarkers of AD pathophysiology to be translated to blood (e.g., phosphorylated tau, amyloid-β and neurofilament light). In this chapter, we review where we stand with both core and novel CSF biomarkers, as well as the explosion of data on blood biomarkers. Also, we discuss potential applications in research aiming to better understand the disease, as well as possible use in routine clinical practice and therapeutic trials.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Some plasma biomarkers such as p-tau have strong associations with brain pathology.
“Despite this, some plasma biomarkers such as p‐tau do have strong associations with brain pathology. 2”
From A genetic and proteomic comparison of key AD biomarkers across tissues (2024) · cites this paper as [2]
Plasma is an alternative biofluid being pursued for AD biomarkers due to its ease of access and low risk of complications.
“One alternative biofluid being pursued for AD biomarkers is blood plasma due to its ease of access and low risk of complications. 2”
From A genetic and proteomic comparison of key AD biomarkers across tissues (2024) · cites this paper as [2]
Advancements in assay sensitivity now enable accurate measurement of many brain-derived proteins present in blood at low concentrations.
“In addition, advancements in assay sensitivity now enable accurate measurement of many brain‐derived proteins that are present in blood at low concentrations. 2”
From A genetic and proteomic comparison of key AD biomarkers across tissues (2024) · cites this paper as [2]
Cites
Neuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123 · see citing works
NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease
Jack, C. R., Bennett, D. A., Blennow, K., Carrillo, M. C., Dunn, B., Haeberlein, S. B., Holtzman, D. M., Jagust, W., Jessen, F., Karlawish, J., et al. (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.02.018 · Cited by 10,537 · see citing works
Self-citationThe amyloid hypothesis of Alzheimer's disease at 25 years
Selkoe, D. J., & Hardy, J. (2016) · EMBO Molecular Medicine · doi:10.15252/emmm.201606210 · Cited by 6,164 · see citing works
Cryo-EM structures of tau filaments from Alzheimer’s disease
Fitzpatrick, A. W. P., Falcon, B., He, S., Murzin, A. G., Murshudov, G., Garringer, H. J., Crowther, R. A., Ghetti, B., Goedert, M., & Scheres, S. H. W. (2017) · Nature · doi:10.1038/nature23002 · Cited by 2,061 · see citing works
The Cellular Phase of Alzheimer’s Disease
De Strooper, B., & Karran, E. (2016) · Cell · doi:10.1016/j.cell.2015.12.056 · Cited by 1,990 · see citing works
Microglia in Alzheimer’s disease
Hansen, D. V., Hanson, J. E., & Sheng, M. (2018) · Journal of Cell Biology · doi:10.1083/jcb.201709069 · Cited by 1,935 · see citing works
Donanemab in Early Alzheimer’s Disease
Mintun, M. A., Lo, A. C., Duggan Evans, C., Wessels, A. M., Ardayfio, P. A., Andersen, S. W., Shcherbinin, S., Sparks, J., Sims, J. R., Brys, M., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2100708 · Cited by 1,728 · see citing works
High performance plasma amyloid-β biomarkers for Alzheimer's disease
Nakamura, A., Kaneko, N., Villemagne, V. L., Kato, T., Doecke, J., Doré, V., Fowler, C., Li, Q.-X., Martins, R., Rowe, C., et al. (2018) · Nature · doi:10.1038/nature25456 · Cited by 1,681 · see citing works
CSF Biomarkers and Incipient Alzheimer Disease in Patients With Mild Cognitive Impairment
Mattsson, N. (2009) · JAMA · doi:10.1001/jama.2009.1064 · Cited by 1,176 · see citing works
Beach, T. G., Monsell, S. E., Phillips, L. E., & Kukull, W. (2012) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e31824b211b · Cited by 1,103 · see citing works
Clinical diagnosis of Alzheimer’s disease: Recommendations of the International Working Group
Dubois, B., Villain, N., Frisoni, G. B., Rabinovici, G. D., Sabbagh, M., Cappa, S., Bejanin, A., Bombois, S., Epelbaum, S., Teichmann, M., et al. (2021) · The Lancet Neurology · doi:10.1016/s1474-4422(21)00066-1 · Cited by 1,051 · see citing works
Self-citationSwanson, C. J., Zhang, Y., Dhadda, S., Wang, J., Kaplow, J., Lai, R. Y. K., Lannfelt, L., Bradley, H., Rabe, M., Koyama, A., et al. (2021) · Alzheimer's Research & Therapy · doi:10.1186/s13195-021-00813-8 · Cited by 847 · see citing works
Hansson, O., Seibyl, J., Stomrud, E., Zetterberg, H., Trojanowski, J. Q., Bittner, T., Lifke, V., Corradini, V., Eichenlaub, U., Batrla, R., et al. (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.01.010 · Cited by 808 · see citing works
Self-citationBridel, C., van Wieringen, W. N., Zetterberg, H., Tijms, B. M., Teunissen, C. E., and the NFL Group, Alvarez-Cermeño, J. C., Andreasson, U., Axelsson, M., Bäckström, D. C., et al. (2019) · JAMA Neurology · doi:10.1001/jamaneurol.2019.1534 · Cited by 764 · see citing works
Self-citationThijssen, E. H., La Joie, R., Strom, A., Fonseca, C., Iaccarino, L., Wolf, A., Spina, S., Allen, I. E., Cobigo, Y., Heuer, H., et al. (2021) · The Lancet Neurology · doi:10.1016/s1474-4422(21)00214-3 · Cited by 607 · see citing works
Self-citationTau Kinetics in Neurons and the Human Central Nervous System
Sato, C., Barthélemy, N. R., Mawuenyega, K. G., Patterson, B. W., Gordon, B. A., Jockel-Balsarotti, J., Sullivan, M., Crisp, M. J., Kasten, T., Kirmess, K. M., et al. (2018) · Neuron · doi:10.1016/j.neuron.2018.02.015 · Cited by 586 · see citing works
Ovod, V., Ramsey, K. N., Mawuenyega, K. G., Bollinger, J. G., Hicks, T., Schneider, T., Sullivan, M., Paumier, K., Holtzman, D. M., Morris, J. C., et al. (2017) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2017.06.2266 · Cited by 585 · see citing works
Head-to-Head Comparison of 8 Plasma Amyloid-β 42/40 Assays in Alzheimer Disease
Janelidze, S., Teunissen, C. E., Zetterberg, H., Allué, J. A., Sarasa, L., Eichenlaub, U., Bittner, T., Ovod, V., Verberk, I. M. W., Toba, K., et al. (2021) · JAMA Neurology · doi:10.1001/jamaneurol.2021.3180 · Cited by 494 · see citing works
Self-citationMicroglia use TAM receptors to detect and engulf amyloid β plaques
Huang, Y., Happonen, K. E., Burrola, P. G., O’Connor, C., Hah, N., Huang, L., Nimmerjahn, A., & Lemke, G. (2021) · Nature Immunology · doi:10.1038/s41590-021-00913-5 · Cited by 483 · see citing works
Palmqvist, S., Mattsson, N., Hansson, O., & Initiative, F. T. A. D. N. (2016) · Brain · doi:10.1093/brain/aww015 · Cited by 400 · see citing works
Lantero Rodriguez, J., Karikari, T. K., Suárez-Calvet, M., Troakes, C., King, A., Emersic, A., Aarsland, D., Hye, A., Zetterberg, H., Blennow, K., et al. (2020) · Acta Neuropathologica · doi:10.1007/s00401-020-02195-x · Cited by 350 · see citing works
Self-citationInitiative, F. T. A. D. N., Suárez-Calvet, M., Morenas-Rodríguez, E., Kleinberger, G., Schlepckow, K., Araque Caballero, M. Á., Franzmeier, N., Capell, A., Fellerer, K., Nuscher, B., et al. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-018-0301-5 · Cited by 347 · see citing works
NPTX2 and cognitive dysfunction in Alzheimer’s Disease
Xiao, M.-F., Xu, D., Craig, M. T., Pelkey, K. A., Chien, C.-C., Shi, Y., Zhang, J., Resnick, S., Pletnikova, O., Salmon, D., et al. (2017) · eLife · doi:10.7554/elife.23798 · Cited by 316 · see citing works
Ossenkoppele, R., Smith, R., Mattsson-Carlgren, N., Groot, C., Leuzy, A., Strandberg, O., Palmqvist, S., Olsson, T., Jögi, J., Stormrud, E., et al. (2021) · JAMA Neurology · doi:10.1001/jamaneurol.2021.1858 · Cited by 311 · see citing works
CSF biomarkers for Alzheimer disease correlate with cortical brain biopsy findings
Seppälä, T. T., Nerg, O., Koivisto, A. M., Rummukainen, J., Puli, L., Zetterberg, H., Pyykkö, O. T., Helisalmi, S., Alafuzoff, I., Hiltunen, M., et al. (2012) · Neurology · doi:10.1212/wnl.0b013e3182563bd0 · Cited by 236 · see citing works
Self-citationDiagnostic value of cerebrospinal fluid alpha-synuclein seed quantification in synucleinopathies
Poggiolini, I., Gupta, V., Lawton, M., Lee, S., El-Turabi, A., Querejeta-Coma, A., Trenkwalder, C., Sixel-Döring, F., Foubert-Samier, A., Pavy-Le Traon, A., et al. (2022) · Brain · doi:10.1093/brain/awab431 · Cited by 191 · see citing works
The pre-synaptic vesicle protein synaptotagmin is a novel biomarker for Alzheimer’s disease
Öhrfelt, A., Brinkmalm, A., Dumurgier, J., Brinkmalm, G., Hansson, O., Zetterberg, H., Bouaziz-Amar, E., Hugon, J., Paquet, C., & Blennow, K. (2016) · Alzheimer's Research & Therapy · doi:10.1186/s13195-016-0208-8 · Cited by 184 · see citing works
Self-citationSutphen, C. L., McCue, L., Herries, E. M., Xiong, C., Ladenson, J. H., Holtzman, D. M., Fagan, A. M., & On behalf of, A. D. N. I. (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.01.012 · Cited by 162 · see citing works
Gobom, J., Parnetti, L., Rosa-Neto, P., Vyhnalek, M., Gauthier, S., Cataldi, S., Lerch, O., Laczo, J., Cechova, K., Clarin, M., et al. (2022) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm-2021-0651 · Cited by 146 · see citing works
Self-citationScialò, C., Tran, T. H., Salzano, G., Novi, G., Caponnetto, C., Chiò, A., Calvo, A., Canosa, A., Moda, F., Caroppo, P., et al. (2020) · Brain Communications · doi:10.1093/braincomms/fcaa142 · Cited by 123 · see citing works
O’Connor, A., Karikari, T. K., Poole, T., Ashton, N. J., Lantero Rodriguez, J., Khatun, A., Swift, I., Heslegrave, A. J., Abel, E., Chung, E., et al. (2021) · Molecular Psychiatry · doi:10.1038/s41380-020-0838-x · Cited by 122 · see citing works
Self-citationMild to moderate Alzheimer dementia with insufficient neuropathological changes
Serrano‐Pozo, A., Qian, J., Monsell, S. E., Blacker, D., Gómez‐Isla, T., Betensky, R. A., Growdon, J. H., Johnson, K. A., Frosch, M. P., Sperling, R. A., et al. (2014) · Annals of Neurology · doi:10.1002/ana.24125 · Cited by 120 · see citing works
Emerging cerebrospinal fluid biomarkers in autosomal dominant Alzheimer's disease
Schindler, S. E., Li, Y., Todd, K. W., Herries, E. M., Henson, R. L., Gray, J. D., Wang, G., Graham, D. L., Shaw, L. M., Trojanowski, J. Q., et al. (2019) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.12.019 · Cited by 101 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Biomarker Changes during 20 Years Preceding Alzheimer’s Disease
Jia, J., Ning, Y., Chen, M., Wang, S., Yang, H., Li, F., Ding, J., Li, Y., Zhao, B., Lyu, J., et al. (2024) · New England Journal of Medicine · doi:10.1056/nejmoa2310168 · Cited by 455 · see citing works
A genetic and proteomic comparison of key AD biomarkers across tissues
Marsh, T. W., Western, D., Timsina, J., Gorijala, P., Yang, C., Pastor, P., Liu, M., Morris, J. C., Bateman, R. J., Schindler, S. E., et al. (2024) · Alzheimer's & Dementia · doi:10.1002/alz.14139 · Cited by 6 · see citing works
- Authors
- Simrén, J., Elmgren, A., Blennow, K., & Zetterberg, H.
- Affiliations
- Sahlgrenska University Hospital (SE)
- Corresponding author
- Simrén, Joel
- Venue
- Advances in Clinical Chemistry
- Publisher
- Elsevier
- Published
- 2023
- Volume
- 112
- Pages
- 249-281
- ISSN
- 0065-2423 (ISSN-L)
- OpenAlex
- W4312826327
- Cited by
- 58
- References
- 33
- Citations by year
- 2026: 20 · 2025: 18 · 2024: 14 · 2023: 6
- FWCI
- 50.93
- Type
- book chapter
- Language
- en
- Open access
- closed
- Licence
- Locations
- Advances in clinical chemistry (publishedVersion)
- PubMed (publishedVersion)
- 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, cerebrospinal fluid biomarkers, blood biomarkers, amyloid-beta, tau protein, neurodegeneration, phosphorylated tau, neurofilament light chain, synaptic pathology, neuroinflammation, disease-modifying therapy, clinical translation of biomarkers
- MeSH terms
- Alzheimer Disease, Humans, Peptide Fragments, Biomarkers, Amyloid beta-Peptides, tau Proteins
About these checks
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
