Login Register Cart 0
Generic placeholder image

Current Alzheimer Research

Editor-in-Chief

ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Follow-up Comparisons of Two Plasma Biomarkers of Alzheimer’s Disease, Neurofilament Light Chain, and Oligomeric Aβ: A Pilot Study

Author(s): YongSoo Shim*

Volume 20, Issue 10, 2023

Published on: 30 January, 2024

Page: [715 - 724] Pages: 10

DOI: 10.2174/0115672050284054240119101834

Price: $65

Abstract

Background and Objective: Recent evidence suggests that blood-based biomarkers might be useful for Alzheimer’s disease (AD). Among them, we intend to investigate whether neurofilament light (NfL) and multimer detection system-oligomeric Aβ (MDS-OAβ) values can be useful in screening, predicting, and monitoring disease progression and how the relationship between NfL and MDS-OAβ values changes.

Methods: Eighty participants with probable AD dementia, 50 with mild cognitive impairment (MCI), and 19 with subjective cognitive decline (SCD) underwent baseline and follow-up evaluations of the Mini-Mental Status Examination (MMSE) and both plasma biomarkers.

Results: Baseline MDS-OAß (p = 0.016) and NfL (p = 0.002) plasma concentrations differed significantly among groups, but only NfL correlated with baseline MMSE scores (r = -0.278, p = 0.001). In follow-up, neither correlated with MMSE changes overall. However, in SCD and MCI participants (n = 32), baseline MDS-OAß correlated with follow-up MMSE scores (r = 0.532, p = 0.041). Linear regression revealed a relationship between baseline MDS-OAβ and follow-up MMSE scores. In SCD and MCI participants, plasma NfL changes correlated with MMSE changes (r = 0.564, p = 0.028).

Conclusion: This study shows that only in participants with SCD and MCI, not including AD dementia, can MDS-OAß predict the longitudinal cognitive decline measured by follow-up MMSE. Changes of NfL, not MDS-OAß, parallel the changes of MMSE. Further studies with larger samples and longer durations could strengthen these results..

« Previous Next »
[1]
Scheltens P, De Strooper B, Kivipelto M, et al. Alzheimer’s disease. Lancet 2021; 397(10284): 1577-90.
[http://dx.doi.org/10.1016/S0140-6736(20)32205-4] [PMID: 33667416]
[2]
Hansson O. Biomarkers for neurodegenerative diseases. Nat Med 2021; 27(6): 954-63.
[http://dx.doi.org/10.1038/s41591-021-01382-x] [PMID: 34083813]
[3]
Jack CR Jr, Bennett DA, Blennow K, et al. NIA‐AA research framework: Toward a biological definition of alzheimer’s disease. Alzheimers Dement 2018; 14(4): 535-62.
[http://dx.doi.org/10.1016/j.jalz.2018.02.018] [PMID: 29653606]
[4]
Blennow K. Phenotyping alzheimer’s disease with blood tests. Science 2021; 373(6555): 626-8.
[http://dx.doi.org/10.1126/science.abi5208] [PMID: 34353941]
[5]
Teunissen CE, Verberk IMW, Thijssen EH, et al. Blood-based biomarkers for alzheimer’s disease: Towards clinical implementation. Lancet Neurol 2022; 21(1): 66-77.
[http://dx.doi.org/10.1016/S1474-4422(21)00361-6] [PMID: 34838239]
[6]
Thijssen EH, La Joie R, Wolf A, et al. Diagnostic value of plasma phosphorylated tau181 in Alzheimer’s disease and frontotemporal lobar degeneration. Nat Med 2020; 26(3): 387-97.
[http://dx.doi.org/10.1038/s41591-020-0762-2] [PMID: 32123386]
[7]
Palmqvist S, Janelidze S, Quiroz YT, et al. Discriminative accuracy of plasma phospho-tau217 for alzheimer disease vs. other neurodegenerative disorders. JAMA 2020; 324(8): 772-81.
[http://dx.doi.org/10.1001/jama.2020.12134] [PMID: 32722745]
[8]
O’Connor A, Karikari TK, Poole T, et al. Plasma phospho-tau181 in presymptomatic and symptomatic familial Alzheimer’s disease: A longitudinal cohort study. Mol Psychiatry 2021; 26(10): 5967-76.
[http://dx.doi.org/10.1038/s41380-020-0838-x] [PMID: 32665603]
[9]
Lantero RJ, Karikari TK, Suárez-Calvet M, et al. Plasma p-tau181 accurately predicts alzheimer’s disease pathology at least 8 years prior to post-mortem and improves the clinical characterisation of cognitive decline. Acta Neuropathol 2020; 140(3): 267-78.
[http://dx.doi.org/10.1007/s00401-020-02195-x] [PMID: 32720099]
[10]
Karikari TK, Pascoal TA, Ashton NJ, et al. Blood phosphorylated tau 181 as a biomarker for alzheimer’s disease: A diagnostic performance and prediction modelling study using data from four prospective cohorts. Lancet Neurol 2020; 19(5): 422-33.
[http://dx.doi.org/10.1016/S1474-4422(20)30071-5] [PMID: 32333900]
[11]
Janelidze S, Mattsson N, Palmqvist S, et al. Plasma P-tau181 in alzheimer’s disease: Relationship to other biomarkers, differential diagnosis, neuropathology and longitudinal progression to alzheimer’s dementia. Nat Med 2020; 26(3): 379-86.
[http://dx.doi.org/10.1038/s41591-020-0755-1] [PMID: 32123385]
[12]
Vergallo A, Mégret L, Lista S, et al. Plasma amyloid β 40/42 ratio predicts cerebral amyloidosis in cognitively normal individuals at risk for alzheimer’s disease. Alzheimers Dement 2019; 15(6): 764-75.
[http://dx.doi.org/10.1016/j.jalz.2019.03.009] [PMID: 31113759]
[13]
Schindler SE, Bollinger JG, Ovod V, et al. High-precision plasma β-amyloid 42/40 predicts current and future brain amyloidosis. Neurology 2019; 93(17): e1647-59.
[http://dx.doi.org/10.1212/WNL.0000000000008081] [PMID: 31371569]
[14]
Risacher SL, Fandos N, Romero J, et al. Plasma amyloid beta levels are associated with cerebral amyloid and tau deposition. Alzheimers Dement 2019; 11(1): 510-9.
[http://dx.doi.org/10.1016/j.dadm.2019.05.007] [PMID: 31384662]
[15]
Ashton NJ, Nevado-Holgado AJ, Barber IS, et al. A plasma protein classifier for predicting amyloid burden for preclinical alzheimer’s disease. Sci Adv 2019; 5(2): eaau7220.
[http://dx.doi.org/10.1126/sciadv.aau7220] [PMID: 30775436]
[16]
Nakamura A, Kaneko N, Villemagne VL, et al. High performance plasma amyloid-β biomarkers for alzheimer’s disease. Nature 2018; 554(7691): 249-54.
[http://dx.doi.org/10.1038/nature25456] [PMID: 29420472]
[17]
Barthélemy NR, Horie K, Sato C, Bateman RJ. Blood plasma phosphorylated-tau isoforms track CNS change in alzheimer’s disease. J Exp Med 2020; 217(11): e20200861.
[http://dx.doi.org/10.1084/jem.20200861] [PMID: 32725127]
[18]
Karikari TK, Benedet AL, Ashton NJ, et al. Diagnostic performance and prediction of clinical progression of plasma phospho-tau181 in the alzheimer’s disease neuroimaging initiative. Mol Psychiatry 2021; 26(2): 429-42.
[http://dx.doi.org/10.1038/s41380-020-00923-z] [PMID: 33106600]
[19]
Fandos N, Pérez-Grijalba V, Pesini P, et al. Plasma amyloid β 42/40 ratios as biomarkers for amyloid β cerebral deposition in cognitively normal individuals. Alzheimers Dement 2017; 8(1): 179-87.
[http://dx.doi.org/10.1016/j.dadm.2017.07.004] [PMID: 28948206]
[20]
Mattsson N, Andreasson U, Zetterberg H, Blennow K. Association of plasma neurofilament light with neurodegeneration in patients with alzheimer disease. JAMA Neurol 2017; 74(5): 557-66.
[http://dx.doi.org/10.1001/jamaneurol.2016.6117] [PMID: 28346578]
[21]
Ovod V, Ramsey KN, Mawuenyega KG, et al. Amyloid β concentrations and stable isotope labeling kinetics of human plasma specific to central nervous system amyloidosis. Alzheimers Dement 2017; 13(8): 841-9.
[http://dx.doi.org/10.1016/j.jalz.2017.06.2266] [PMID: 28734653]
[22]
Weston PSJ, Poole T, Ryan NS, et al. Serum neurofilament light in familial alzheimer disease. Neurology 2017; 89(21): 2167-75.
[http://dx.doi.org/10.1212/WNL.0000000000004667] [PMID: 29070659]
[23]
Mielke MM, Hagen CE, Xu J, et al. Plasma phospho‐tau181 increases with alzheimer’s disease clinical severity and is associated with tau‐ and amyloid‐positron emission tomography. Alzheimers Dement 2018; 14(8): 989-97.
[http://dx.doi.org/10.1016/j.jalz.2018.02.013] [PMID: 29626426]
[24]
Hampel H, O’Bryant SE, Molinuevo JL, et al. Blood-based biomarkers for alzheimer disease: Mapping the road to the clinic. Nat Rev Neurol 2018; 14(11): 639-52.
[http://dx.doi.org/10.1038/s41582-018-0079-7] [PMID: 30297701]
[25]
Petzold A. Neurofilament phosphoforms: Surrogate markers for axonal injury, degeneration and loss. J Neurol Sci 2005; 233(1-2): 183-98.
[http://dx.doi.org/10.1016/j.jns.2005.03.015] [PMID: 15896809]
[26]
Barro C, Benkert P, Disanto G, et al. Serum neurofilament as a predictor of disease worsening and brain and spinal cord atrophy in multiple sclerosis. Brain 2018; 141(8): 2382-91.
[http://dx.doi.org/10.1093/brain/awy154] [PMID: 29860296]
[27]
Bacioglu M, Maia LF, Preische O, et al. Neurofilament light chain in blood and CSF as marker of disease progression in mouse models and in neurodegenerative diseases. Neuron 2016; 91(1): 56-66.
[http://dx.doi.org/10.1016/j.neuron.2016.05.018] [PMID: 27292537]
[28]
Brureau A, Blanchard-Bregeon V, Pech C, et al. NF-L in cerebrospinal fluid and serum is a biomarker of neuronal damage in an inducible mouse model of neurodegeneration. Neurobiol Dis 2017; 104: 73-84.
[http://dx.doi.org/10.1016/j.nbd.2017.04.007] [PMID: 28392472]
[29]
Kuhle J, Barro C, Disanto G, et al. Serum neurofilament light chain in early relapsing remitting MS is increased and correlates with CSF levels and with MRI measures of disease severity. Mult Scler 2016; 22(12): 1550-9.
[http://dx.doi.org/10.1177/1352458515623365] [PMID: 26754800]
[30]
Zhou W, Zhang J, Ye F, et al. Plasma neurofilament light chain levels in alzheimer’s disease. Neurosci Lett 2017; 650: 60-4.
[http://dx.doi.org/10.1016/j.neulet.2017.04.027] [PMID: 28428015]
[31]
Gisslén M, Price RW, Andreasson U, et al. Plasma concentration of the neurofilament light protein (NFL) is a Biomarker of CNS injury in HIV infection: A cross-sectional study. EBioMedicine 2016; 3: 135-40.
[http://dx.doi.org/10.1016/j.ebiom.2015.11.036] [PMID: 26870824]
[32]
Gaiottino J, Norgren N, Dobson R, et al. Increased neurofilament light chain blood levels in neurodegenerative neurological diseases. PLoS One 2013; 8(9): e75091.
[http://dx.doi.org/10.1371/journal.pone.0075091] [PMID: 24073237]
[33]
Lewczuk P, Ermann N, Andreasson U, et al. Plasma neurofilament light as a potential biomarker of neurodegeneration in alzheimer’s disease. Alzheimers Res Ther 2018; 10(1): 71.
[http://dx.doi.org/10.1186/s13195-018-0404-9] [PMID: 30055655]
[34]
Mazzeo S, Ingannato A, Giacomucci G, et al. Plasma neurofilament light chain predicts Alzheimer’s disease in patients with subjective cognitive decline and mild cognitive impairment: A cross‐sectional and longitudinal study. Eur J Neurol 2024; 31(1): e16089.
[http://dx.doi.org/10.1111/ene.16089] [PMID: 37797300]
[35]
An SSA, Lee B, Yu JS, et al. Dynamic changes of oligomeric amyloid β levels in plasma induced by spiked synthetic Aβ42. Alzheimers Res Ther 2017; 9(1): 86.
[http://dx.doi.org/10.1186/s13195-017-0310-6] [PMID: 29041968]
[36]
Youn YC, Lee BS, Kim GJ, et al. Blood amyloid-β oligomerization as a biomarker of alzheimer’s disease: A blinded validation study. J Alzheimers Dis 2020; 75(2): 493-9.
[http://dx.doi.org/10.3233/JAD-200061] [PMID: 32310175]
[37]
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. Alzheimers Dement 2011; 7(3): 263-9.
[http://dx.doi.org/10.1016/j.jalz.2011.03.005] [PMID: 21514250]
[38]
Albert MS, DeKosky ST, Dickson D, et al. The diagnosis of mild cognitive impairment due to alzheimer’s disease: Recommendations from the national institute on aging‐alzheimer’s association workgroups on diagnostic guidelines for alzheimer’s disease. Alzheimers Dement 2011; 7(3): 270-9.
[http://dx.doi.org/10.1016/j.jalz.2011.03.008] [PMID: 21514249]
[39]
Jessen F, Amariglio RE, van Boxtel M, et al. A conceptual framework for research on subjective cognitive decline in preclinical alzheimer’s disease. Alzheimers Dement 2014; 10(6): 844-52.
[http://dx.doi.org/10.1016/j.jalz.2014.01.001] [PMID: 24798886]
[40]
Ryu HJ, Yang DW. The seoul neuropsychological screening battery (SNSB) for comprehensive neuropsychological assessment. Dement Neurocognitive Disord 2023; 22(1): 1-15.
[http://dx.doi.org/10.12779/dnd.2023.22.1.1] [PMID: 36814700]
[41]
Morris JC. The clinical dementia rating (CDR): Current version and scoring rules. Neurology 1993; 43(11): 2412-4.
[http://dx.doi.org/10.1212/WNL.43.11.2412-a] [PMID: 8232972]
[42]
Folstein MF, Folstein SE, McHugh PR. Mini-mental state. J Psychiatr Res 1975; 12(3): 189-98.
[http://dx.doi.org/10.1016/0022-3956(75)90026-6] [PMID: 1202204]
[43]
Erkinjuntti T. Subcortical ischemic vascular disease and dementia. Int Psychogeriatr 2003; 15(S1) (Suppl. 1): 23-6.
[http://dx.doi.org/10.1017/S1041610203008925] [PMID: 16191213]
[44]
Hyman BT, Phelps CH, Beach TG, et al. National institute on aging-alzheimer’s association guidelines for the neuropathologic assessment of alzheimer’s disease. Alzheimers Dement 2012; 8(1): 1-13.
[http://dx.doi.org/10.1016/j.jalz.2011.10.007] [PMID: 22265587]
[45]
Jack CR Jr, Holtzman DM. Biomarker modeling of alzheimer’s disease. Neuron 2013; 80(6): 1347-58.
[http://dx.doi.org/10.1016/j.neuron.2013.12.003] [PMID: 24360540]
[46]
Joshi AD, Pontecorvo MJ, Clark CM, et al. Performance characteristics of amyloid PET with florbetapir F 18 in patients with alzheimer’s disease and cognitively normal subjects. J Nucl Med 2012; 53(3): 378-84.
[http://dx.doi.org/10.2967/jnumed.111.090340] [PMID: 22331215]
[47]
Clark CM, Schneider JA, Bedell BJ, et al. Use of florbetapir-PET for imaging β-amyloid pathology. JAMA 2011; 305(3): 275-83.
[http://dx.doi.org/10.1001/jama.2010.2008] [PMID: 21245183]
[48]
Pike KE, Savage G, Villemagne VL, et al. -amyloid imaging and memory in non-demented individuals: Evidence for preclinical alzheimer’s disease. Brain 2007; 130(11): 2837-44.
[http://dx.doi.org/10.1093/brain/awm238] [PMID: 17928318]
[49]
De Leon MJ, Mosconi L, Blennow K, et al. Imaging and CSF studies in the preclinical diagnosis of Alzheimer’s disease. Ann N Y Acad Sci 2007; 1097(1): 114-45.
[http://dx.doi.org/10.1196/annals.1379.012] [PMID: 17413016]
[50]
Mattsson N, Zetterberg H, Janelidze S, et al. Plasma tau in alzheimer disease. Neurology 2016; 87(17): 1827-35.
[http://dx.doi.org/10.1212/WNL.0000000000003246] [PMID: 27694257]
[51]
Preische O, Schultz SA, Apel A, et al. Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic alzheimer’s disease. Nat Med 2019; 25(2): 277-83.
[http://dx.doi.org/10.1038/s41591-018-0304-3] [PMID: 30664784]
[52]
de Wolf F, Ghanbari M, Licher S, et al. Plasma tau, neurofilament light chain and amyloid-β levels and risk of dementia; A population-based cohort study. Brain 2020; 143(4): 1220-32.
[http://dx.doi.org/10.1093/brain/awaa054] [PMID: 32206776]
[53]
Jack CR Jr. The transformative potential of plasma phosphorylated tau. Lancet Neurol 2020; 19(5): 373-4.
[http://dx.doi.org/10.1016/S1474-4422(20)30112-5] [PMID: 32333888]
[54]
Toledo JB, Vanderstichele H, Figurski M, et al. Factors affecting Aβ plasma levels and their utility as biomarkers in ADNI. Acta Neuropathol 2011; 122(4): 401-13.
[http://dx.doi.org/10.1007/s00401-011-0861-8] [PMID: 21805181]
[55]
Mehta PD, Pirttila T, Patrick BA, Barshatzky M, Mehta SP. Amyloid β protein 1-40 and 1-42 levels in matched cerebrospinal fluid and plasma from patients with alzheimer disease. Neurosci Lett 2001; 304(1-2): 102-6.
[http://dx.doi.org/10.1016/S0304-3940(01)01754-2] [PMID: 11335065]
[56]
Kuo YM, Kokjohn TA, Kalback W, et al. Amyloid-beta peptides interact with plasma proteins and erythrocytes: implications for their quantitation in plasma. Biochem Biophys Res Commun 2000; 268(3): 750-6.
[http://dx.doi.org/10.1006/bbrc.2000.2222] [PMID: 10679277]
[57]
Kuo YM, Emmerling MR, Lampert HC, et al. High levels of circulating Abeta42 are sequestered by plasma proteins in alzheimer’s disease. Biochem Biophys Res Commun 1999; 257(3): 787-91.
[http://dx.doi.org/10.1006/bbrc.1999.0552] [PMID: 10208861]
[58]
Wang J, Gu BJ, Masters CL, Wang YJ. A systemic view of alzheimer disease — insights from amyloid-β metabolism beyond the brain. Nat Rev Neurol 2017; 13(10): 612-23.
[http://dx.doi.org/10.1038/nrneurol.2017.111] [PMID: 28960209]
[59]
Serem WK, Bett CK, Ngunjiri JN, Garno JC. Studies of the growth, evolution, and self‐aggregation of β‐amyloid fibrils using tapping‐mode atomic force microscopy. Microsc Res Tech 2011; 74(7): 699-708.
[http://dx.doi.org/10.1002/jemt.20940] [PMID: 21698718]
[60]
Tomic JL, Pensalfini A, Head E, Glabe CG. Soluble fibrillar oligomer levels are elevated in alzheimer’s disease brain and correlate with cognitive dysfunction. Neurobiol Dis 2009; 35(3): 352-8.
[http://dx.doi.org/10.1016/j.nbd.2009.05.024] [PMID: 19523517]
[61]
Um JW, Nygaard HB, Heiss JK, et al. Alzheimer amyloid-β oligomer bound to postsynaptic prion protein activates Fyn to impair neurons. Nat Neurosci 2012; 15(9): 1227-35.
[http://dx.doi.org/10.1038/nn.3178] [PMID: 22820466]
[62]
Izzo NJ, Staniszewski A, To L, et al. Alzheimer’s therapeutics targeting amyloid beta 1-42 oligomers I: Abeta 42 oligomer binding to specific neuronal receptors is displaced by drug candidates that improve cognitive deficits. PLoS One 2014; 9(11): e111898.
[http://dx.doi.org/10.1371/journal.pone.0111898] [PMID: 25390368]
[63]
Cline EN, Bicca MA, Viola KL, Klein WL. The Amyloid-β oligomer hypothesis: Beginning of the third decade. J Alzheimers Dis 2018; 64(s1): S567-610.
[http://dx.doi.org/10.3233/JAD-179941] [PMID: 29843241]
[64]
An SSA, Lim KT, Oh HJ, et al. Differentiating blood samples from scrapie infected and non-infected hamsters by detecting disease-associated prion proteins using multimer detection system. Biochem Biophys Res Commun 2010; 392(4): 505-9.
[http://dx.doi.org/10.1016/j.bbrc.2010.01.053] [PMID: 20085753]
[65]
Lim K, Kim SY, Lee B, et al. Magnetic microparticle-based multimer detection system for the detection of prion oligomers in sheep. Int J Nanomedicine 2015; 10(Spec Iss): 241-50.
[PMID: 26425091]
[66]
Pyun JM, Ryu JS, Lee R, et al. Plasma amyloid-β oligomerization tendency predicts amyloid PET positivity. Clin Interv Aging 2021; 16: 749-55.
[http://dx.doi.org/10.2147/CIA.S312473] [PMID: 33958861]
[67]
Youn YC, Kim HR, Shin HW, et al. Prediction of amyloid PET positivity via machine learning algorithms trained with EDTA-based blood amyloid-β oligomerization data. BMC Med Inform Decis Mak 2022; 22(1): 286.
[http://dx.doi.org/10.1186/s12911-022-02024-z] [PMID: 36344984]
[68]
Youn YC, Kang S, Suh J, et al. Blood amyloid-β oligomerization associated with neurodegeneration of alzheimer’s disease. Alzheimers Res Ther 2019; 11(1): 40.
[http://dx.doi.org/10.1186/s13195-019-0499-7] [PMID: 31077246]
[69]
Wang MJ, Yi S, Han J, et al. Oligomeric forms of amyloid-β protein in plasma as a potential blood-based biomarker for Alzheimer’s disease. Alzheimers Res Ther 2017; 9(1): 98.
[http://dx.doi.org/10.1186/s13195-017-0324-0] [PMID: 29246249]
[70]
Teunissen CE, Khalil M. Neurofilaments as biomarkers in multiple sclerosis. Mult Scler 2012; 18(5): 552-6.
[http://dx.doi.org/10.1177/1352458512443092] [PMID: 22492131]
[71]
Scheltens P, Blennow K, Breteler MMB, et al. Alzheimer’s disease. Lancet 2016; 388(10043): 505-17.
[http://dx.doi.org/10.1016/S0140-6736(15)01124-1] [PMID: 26921134]
[72]
Shim Y. Clinical application of plasma neurofilament light chain in a memory clinic: A pilot study. Dement Neurocognitive Disord 2022; 21(2): 59-70.
[http://dx.doi.org/10.12779/dnd.2022.21.2.59] [PMID: 35585907]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy