The meaning of blood and cerebrospinal fluid biomarkers in early diagnosis of Alzheimer's disease

Julita Szarpak, Weronika Dalmata, Ilona Gąbka, Daria Madycka, Olga Wysokińska



Introduction and purpose: Alzheimer's disease (AD) belongs to the group of neurodegenerative diseases and is the leading cause of dementia worldwide. Its development includes the impact of genetic, metabolic and environmental factors. Despite high prevalence of Alzheimer’s disease and dynamic development of medical science, there is currently no clinically proven causal treatment. The proposed therapies are only symptomatic. However, there is a wide set of substances known as biomarkers that are detected in the blood or in the cerebrospinal fluid (CSF) in the stages preceding full-blown Alzheimer's disease.

Brief description of the state of knowledge: In order to obtain material for CSF examination, a lumbar puncture must be performed. It is an invasive procedure, with the risk of complications such as bleeding into the spinal cord, infection or even nerve damage. Obtaining a blood sample for testing specific indicators is less invasive and more widely available. Currently, the diagnostic significance of commonly known markers arising in the progress of the AD pathological process, such as amyloid β, tau protein and its phosphorylated form or β-secretase, is being investigated. As the knowledge on the pathogenesis of AD grows, further markers such as ubiquitin, micro RNA or plasma neurofilament light are tested.

Conclusions: There is a collection of biomarkers that can perform a diagnostic function for Alzheimer's disease. Due to the advantages of blood and plasma testing, basing the diagnosis of early forms of AD on these tests seems to be particularly interesting. However, the use of biomarkers on a global scale requires further research and test standardization, as well as the development of guidelines for their interpretation.


Alzheimer’s disease; blood biomarkers; cerebrospinal fluid biomarkers; dementia

Full Text:


References Accessed August 10, 2020.

McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer’s and Dementia. 2011;7(3):263-269. doi:10.1016/j.jalz.2011.03.005

Alzheimer W. Policy Brief : The Global Impact of Dementia 2013-2050.

Lane CA, Hardy J, Schott JM. Alzheimer’s disease. European Journal of Neurology. 2018;25(1):59-70. doi:10.1111/ene.13439

Oboudiyat C, Glazer H, Seifan A, Greer C, Isaacson R. Alzheimer’s Disease. Seminars in Neurology. 2013;33(04):313-329. doi:10.1055/s-0033-1359319

Eratne D, Loi SM, Farrand S, Kelso W, Velakoulis D, Looi JC. Alzheimer’s disease: clinical update on epidemiology, pathophysiology and diagnosis. Australasian Psychiatry. 2018;26(4):347-357. doi:10.1177/1039856218762308

Masters CL, Bateman R, Blennow K, Rowe CC, Sperling RA, Cummings JL. Alzheimer’s disease. Nature Reviews Disease Primers. 2015;1(1):15056. doi:10.1038/nrdp.2015.56

Potter R, Patterson BW, Elbert DL, et al. Increased in Vivo Amyloid- 42 Production, Exchange, and Loss in Presenilin Mutation Carriers. Science Translational Medicine. 2013;5(189):189ra77-189ra77. doi:10.1126/scitranslmed.3005615

Schneider A, Mandelkow E. Tau-based treatment strategies in neurodegenerative diseases. Neurotherapeutics. 2008;5(3):443-457. doi:10.1016/j.nurt.2008.05.006

Ryman DC, Acosta-Baena N, Aisen PS, et al. Symptom onset in autosomal dominant Alzheimer disease: A systematic review and meta-analysis. Neurology. 2014;83(3):253-260. doi:10.1212/WNL.0000000000000596

Serrano-Pozo A, Qian J, Monsell SE, Betensky RA, Hyman BT. APOE ε2 is associated with milder clinical and pathological Alzheimer disease. Annals of Neurology. 2015;77(6):917-929. doi:10.1002/ana.24369

Scheltens P, Blennow K, Breteler MMB, et al. Alzheimer’s disease. The Lancet. 2016;388(10043):505-517. doi:10.1016/S0140-6736(15)01124-1

Congdon EE, Sigurdsson EM. Tau-targeting therapies for Alzheimer disease. Nature Reviews Neurology. 2018;14(7):399-415. doi:10.1038/s41582-018-0013-z

Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathologica. 1991;82(4):239-259. doi:10.1007/BF00308809

Blennow K. Cerebrospinal fluid protein biomarkers for Alzheimer’s disease. NeuroRX. 2004;1(2):213-225. doi:10.1602/neurorx.1.2.213

Andreasen N, Blennow K. CSF biomarkers for mild cognitive impairment and early Alzheimer’s disease. Clinical Neurology and Neurosurgery. 2005;107(3):165-173. doi:10.1016/j.clineuro.2004.10.011

Braak H, Braak E. Frequency of stages of Alzheimer-related lesions in different age categories. Neurobiology of Aging. 1997;18(4):351-357. doi:10.1016/S0197-4580(97)00056-0

Himmler A, Drechsel D, Kirschner MW, Martin DW. Tau consists of a set of proteins with repeated C-terminal microtubule-binding domains and variable N-terminal domains. Molecular and Cellular Biology. 1989;9(4):1381-1388. doi:10.1128/mcb.9.4.1381

Morris JC. Mild cognitive impairment is early-stage Alzheimer disease: Time to revise diagnostic criteria. Archives of Neurology. 2006;63(1):15-16. doi:10.1001/archneur.63.1.15

Znaczenie biologicznych markerów we wczesnej diagnostyce choroby Alzheimera | Wrocławskie Centrum Alzheimerowskie. Accessed September 9, 2020.

Irizarry MC. Biomarkers of Alzheimer Disease in Plasma. NeuroRx. 2004;1(2):226-234. doi:10.1602/neurorx.1.2.226

Graff-Radford NR, Crook JE, Lucas J, et al. Association of low plasma Aβ42/Aβ40 ratios with increased imminent risk for mild cognitive impairment and Alzheimer disease. Archives of Neurology. 2007;64(3):354-362. doi:10.1001/archneur.64.3.354

Sobów T, Flirski M, Liberski P. Peptydy Aβ w osoczu chorych ze sporadyczną postacią Alzheime- ra u osób z łagodnymi zaburzeniami poznawczymi. Postępy Psychiatrii I Neurologii. 2005;14(2):123-129.

Hartmann S, Zheng F, Kyncl MC, et al. β-Secretase BACE1 Promotes Surface Expression and Function of Kv3.4 at Hippocampal Mossy Fiber Synapses. The Journal of Neuroscience. 2018;38(14):3480-3494. doi:10.1523/JNEUROSCI.2643-17.2018

Decourt B, Sabbagh MN. BACE1 as a potential biomarker for alzheimer’s disease. Journal of Alzheimer’s Disease. 2011;24(SUPPL. 2):53-59. doi:10.3233/JAD-2011-110017

Koelsch G. BACE1 Function and inhibition: Implications of intervention in the amyloid pathway of Alzheimer’s disease pathology. Molecules. 2017;22(10). doi:10.3390/molecules22101723

Zhong Z, Ewers M, Teipel S, et al. Levels of β-secretase (BACE1) in cerebrospinal fluid as a predictor of risk in mild cognitive impairment. Archives of General Psychiatry. 2007;64(6):718-726. doi:10.1001/archpsyc.64.6.718

Holsinger RMD, Lee JS, Boyd A, Masters CL, Collins SJ. CSF BACE1 activity is increased in CJD and Alzheimer disease other dementias. Neurology. 2006;67(4):710-712. doi:10.1212/01.wnl.0000229925.52203.4c

Cao J, Zhong MB, Toro CA, Zhang L, Cai D. Endo-lysosomal pathway and ubiquitin-proteasome system dysfunction in Alzheimer’s disease pathogenesis. Neuroscience Letters. 2019;703:68-78. doi:10.1016/j.neulet.2019.03.016

Blennow K, Zetterberg H. Biomarkers for Alzheimer’s disease: current status and prospects for the future. Journal of Internal Medicine. 2018;284(6):643-663. doi:10.1111/joim.12816

Olsson B, Lautner R, Andreasson U, et al. CSF and blood biomarkers for the diagnosis of Alzheimer’s disease: a systematic review and meta-analysis. The Lancet Neurology. 2016;15(7):673-684. doi:10.1016/S1474-4422(16)00070-3

Lewczuk P, Riederer P, O’Bryant SE, et al. Cerebrospinal fluid and blood biomarkers for neurodegenerative dementias: An update of the Consensus of the Task Force on Biological Markers in Psychiatry of the World Federation of Societies of Biological Psychiatry. World Journal of Biological Psychiatry. 2018;19(4):244-328. doi:10.1080/15622975.2017.1375556

Lashley T, Schott JM, Weston P, et al. Molecular biomarkers of Alzheimer’s disease: progress and prospects. Disease Models & Mechanisms. 2018;11(5):dmm031781. doi:10.1242/dmm.031781

Sadigh-Eteghad S, Sabermarouf B, Majdi A, Talebi M, Farhoudi M, Mahmoudi J. Amyloid-beta: A crucial factor in Alzheimer’s disease. Medical Principles and Practice. 2015;24(1):1-10. doi:10.1159/000369101

Toledo JB, Vanderstichele H, Figurski M, et al. Factors affecting Aβ plasma levels and their utility as biomarkers in ADNI. Acta Neuropathologica. 2011;122(4):401. doi:10.1007/s00401-011-0861-8

Lue LF, Guerra A, Walker DG. Amyloid Beta and Tau as Alzheimer’s Disease Blood Biomarkers: Promise From New Technologies. Neurology and Therapy. 2017;6(Suppl 1):25-36. doi:10.1007/s40120-017-0074-8

Fiandaca MS, Kapogiannis D, Mapstone M, et al. Identification of preclinical Alzheimer’s disease by a profile of pathogenic proteins in neurally derived blood exosomes: A case-control study. Alzheimer’s and Dementia. 2015;11(6):600-607.e1. doi:10.1016/j.jalz.2014.06.008

Sun P, Liu DZ, Jickling GC, Sharp FR, Yin K-J. MicroRNA-based therapeutics in central nervous system injuries. Journal of Cerebral Blood Flow & Metabolism. 2018;38(7):1125-1148. doi:10.1177/0271678X18773871

Zhang YH, Bai SF, Yan JQ. Blood circulating miRNAs as biomarkers of Alzheimer’s disease: A systematic review and meta-analysis. Biomarkers in Medicine. 2019;13(12):1047-1056. doi:10.2217/bmm-2018-0341

Wu Y, Wang Z, Jia X, et al. Prediction of Alzheimer’s disease with serum lipid levels in Asian individuals: a meta-analysis. Biomarkers. 2019;24(4):341-351. doi:10.1080/1354750X.2019.1571633

Rhoads JP, Major AS. How oxidized low-density lipoprotein activates inflammatory responses. Critical Reviews in Immunology. 2018;38(4):333-342. doi:10.1615/CritRevImmunol.2018026483

Li F, Wang Y, Yang H, et al. The effect of BACE1-AS on β-amyloid generation by regulating BACE1 mRNA expression. BMC Molecular Biology. 2019;20(1). doi:10.1186/s12867-019-0140-0

Fotuhi SN, Khalaj-Kondori M, Hoseinpour Feizi MA, Talebi M. Long Non-coding RNA BACE1-AS May Serve as an Alzheimer’s Disease Blood-Based Biomarker. Journal of Molecular Neuroscience. 2019;69(3):351-359. doi:10.1007/s12031-019-01364-2

Zetterberg H, Burnham SC. Blood-based molecular biomarkers for Alzheimer’s disease. Molecular Brain. 2019;12(1). doi:10.1186/s13041-019-0448-1

Mattsson N, Cullen NC, Andreasson U, Zetterberg H, Blennow K. Association between Longitudinal Plasma Neurofilament Light and Neurodegeneration in Patients with Alzheimer Disease. JAMA Neurology. 2019;76(7):791-799. doi:10.1001/jamaneurol.2019.0765

Park JC, Han SH, Mook-Jung I. Peripheral inflammatory biomarkers in Alzheimer’s disease: a brief review. BMB reports. 2020;53(1):10-19. doi:10.5483/bmbrep.2020.53.1.309

Stevenson A, Lopez D, Khoo P, Kalaria RN, Mukaetova-Ladinska EB. Exploring Erythrocytes as Blood Biomarkers for Alzheimer’s Disease. Journal of Alzheimer’s Disease. 2017;60(3):845-857. doi:10.3233/JAD-170363

Article Metrics

Metrics Loading ...

Metrics powered by PLOS ALM

Journal of Education, Health and Sport formerly Journal of Health Sciences

Declaration on the original version.

Editors indicates that the main version of the magazine is to issue a "electronic".

The journal has had 5 points in Ministry of Science and Higher Education parametric evaluation. § 8. 2) and § 12. 1. 2) 22.02.2019.

1223 Journal of Education, Health and Sport eISSN 2391-8306 7

ISSN 2391-8306 formerly ISSN: 1429-9623 / 2300-665X

Archives 2011 - 2014

PBN 2011 - 2014

POL-index 2011 - 2014

BASE 2011 - 2014

Indexed in Bases, Bazy indeksacyjne: ERIH Plus, Worldcat, PBN/POL-Index, ICI Journals Master List, Directory of Open Access Journals (DOAJ), ZBD, Ulrich's periodicals, Google Scholar, Polska Bibliografia Lekarska, EuroPub database, NLM Catalog Result - NCBI, BASE, Russian Sciences Index, Arianta.

US NLM = 101679844

101679844 - NLM Catalog Result - NCBI

Find a library that holds this journal:


PBN Poland



Redaction, Publisher and Editorial Office

Publisher and Editorial Office
Department of Physical Culture,
Faculty of Earth Sciences and Spatial Management,
Nicolaus Copernicus University in Toruń, Poland
Address: Str. Lwowska 1, 87-100 Toruń, Poland

  Open Access ISSN 2391-8306 formerly ISSN: 1429-9623 / 2300-665X

The journal has been approved for inclusion in ERIH PLUS.

The ERIH PLUS listing of the journal is available at

Indexed in Index Copernicus Journals Master List.,p24782242,3.html

ICV 2019 = 100.00 ICV 2018 = 95.95 ICV 2017 = 91.30 ICV 2016 = 84.69 ICV 2015 = 93.34 ICV 2014 = 89.51 Standardized Value: 8.27 ICV 2013: 7.32 ICV 2012: 6.41 ICV 20115.48

RG Journal Impact: 0.18 *

*This value is calculated using ResearchGate data and is based on average citation counts from work published in this journal. The data used in the calculation may not be exhaustive.

RG Journal impact history

2020Available summer 2021
2018 / 20190.18

RG Journal impact over time

RG Journal impact

Indexed in Polish Scholarly Bibliography (PBN) (PBN Polska Bibliografia Naukowa) (

is a portal of the Polish Ministry of Science and Higher Education, collecting information on publications of Polish scientists and on Polish and foreign scholarly journals. Polish Scholarly Bibliograhpy is a part of POL-on - System of Information on Higher Education. It is operated by the Interdisciplinary Centre for Mathematical and Computational Modelling, University of Warsaw.

Indexed in Russian Sciences Index Российский индекс научного цитирования (РИНЦ)

Indexed in Arianta Polish scientific and professional electronic journals Aneta Drabek i Arkadiusz Pulikowski


Partnerzy platformy czasopism