Amyloid Beta as a Candidate Blood Biomarker of Early Cognitive Decline in the Elderly—A Preliminary Study
Abstract
1. Introduction
2. Material and Methods
2.1. Material
2.2. Biochemical Analysis
2.3. Socioclinical Analysis
2.4. Statistical Analysis
3. Results
3.1. Socioclinical Analysis
3.2. Aβ42 Plasma Levels
Cognitive Status | ANOVA K-W p Level | |||
---|---|---|---|---|
Norm | MCI | Mild Dementia | ||
Amyloid-β 42 | 62.8 [32.8–102.4] | 73.5 [42.4–104.5] | 51.6 [21.2–92.6] | 0.198 |
Gender | U M-W p Level | ||
---|---|---|---|
Female | Male | ||
Amyloid-β 42 | 62.1 [29.0–93.7] | 62.8 [31.8–104.0] | 0.862 |
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Correction Statement
References
- GBD 2019. Dementia Forecasting Collaborators, Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: An analysis for the Global Burden of Disease Study 2019. Lancet Public Health 2022, 7, e105–e125. [CrossRef]
- Chen, S.; Cao, Z.; Nandi, A.; Counts, N.; Jiao, L.; Prettner, K.; Kuhn, M.; Seligman, B.; Tortorice, D.; Vigo, D.; et al. The global macroeconomic burden of Alzheimer’s disease and other dementias: Estimates and projections for 152 countries or territories. Lancet Glob. Health 2024, 12, e1534–e1543. [Google Scholar] [CrossRef]
- Blennow, K.; Mattsson, N.; Schöll, M.; Hansson, O.; Zetterberg, H. Amyloid biomarkers in Alzheimer’s disease. Trends Pharmacol. Sci. 2015, 36, 297–309. [Google Scholar] [CrossRef] [PubMed]
- Nabers, A.; Perna, L.; Lange, J.; Mons, U.; Schartner, J.; Güldenhaupt, J.; Saum, K.-U.; Janelidze, S.; Holleczek, B.; Rujescu, D.; et al. Amyloid blood biomarker detects Alzheimer’s disease. EMBO Mol. Med. 2018, 10, e8763. [Google Scholar] [CrossRef] [PubMed]
- Lista, S.; Faltraco, F.; Prvulovic, D.; Hampel, H. Blood and plasma-based proteomic biomarker research in Alzheimer’s disease. Prog. Neurobiol. 2013, 101–102, 1–17. [Google Scholar] [CrossRef]
- O’Bryant, S.E.; Edwards, M.; Johnson, L.; Hall, J.; Villarreal, A.E.; Britton, G.B.; Quiceno, M.; Cullum, C.M.; Graff-Radford, N.R. A blood screening test for Alzheimer’s disease. Alzheimers Dement. 2016, 3, 83–90. [Google Scholar] [CrossRef]
- O’Bryant, S.E.; Mielke, M.M.; Rissman, R.A.; Lista, S.; Vanderstichele, H.; Zetterberg, H.; Lewczuk, P.; Posner, H.; Hall, J.; Johnson, L.; et al. Blood-based biomarkers in Alzheimer disease: Current state of the science and a novel collaborative paradigm for advancing from discovery to clinic. Alzheimers Dement. 2017, 13, 45–58. [Google Scholar] [CrossRef] [PubMed]
- Molinuevo, J.L.; Ayton, S.; Batrla, R.; Bednar, M.M.; Bittner, T.; Cummings, J.; Fagan, A.M.; Hampel, H.; Mielke, M.M.; Mikulskis, A.; et al. Current state of Alzheimer’s fluid biomarkers. Acta Neuropathol. 2018, 136, 821–853. [Google Scholar] [CrossRef]
- Henriksen, K.; O’Bryant, S.E.; Hampel, H.; Trojanowski, J.Q.; Montine, T.J.; Jeromin, A.; Blennow, K.; Lönneborg, A.; Wyss-Coray, T.; Soares, H.; et al. The future of blood-based biomarkers for Alzheimer’s disease. Alzheimers Dement. 2014, 10, 115–131. [Google Scholar] [CrossRef]
- Schneider, P.; Hampel, H.; Buerger, K. Biological marker candidates of Alzheimer’s disease in blood, plasma, and serum. CNS Neurosci. Ther. 2009, 15, 358–374. [Google Scholar] [CrossRef]
- Snyder, H.M.; Carrillo, M.C.; Grodstein, F.; Henriksen, K.; Jeromin, A.; Lovestone, S.; Mielke, M.M.; O’Bryant, S.; Sarasa, M.; Sjøgren, M.; et al. Developing novel blood-based biomarkers for Alzheimer’s disease. Alzheimers Dement. 2014, 10, 109–114. [Google Scholar] [CrossRef]
- O’Bryant, S.E. Introduction to special issue on Advances in blood-based biomarkers of Alzheimer’s disease. Alzheimers Dement. 2016, 3, 110–112. [Google Scholar] [CrossRef] [PubMed]
- Hiltunen, M.; van Groen, T.; Jolkkonen, J. Functional roles of amyloid-beta protein precursor and amyloid-beta peptides: Evidence from experimental studies. J. Alzheimers Dis. 2009, 18, 401–412. [Google Scholar] [CrossRef] [PubMed]
- Tabaton, M.; Zhu, X.; Perry, G.; Smith, M.A.; Giliberto, L. Signaling effect of amyloid-beta (42) on the processing of AβPP. Exp. Neurol. 2010, 221, 18–25. [Google Scholar] [CrossRef]
- Baruch-Suchodolsky, R.; Fischer, B. Aβ40, either soluble or aggregated, is a remarkably potent antioxidant in cell-free oxidative systems. Biochemistry 2009, 48, 4354–4370. [Google Scholar] [CrossRef]
- Igbavboa, U.; Sun, G.Y.; Weisman, G.A.; He, Y.; Wood, W.G. Amyloid beta-protein stimulates trafficking of cholesterol and caveolin-1 from the plasma membrane to the Golgi complex in mouse primary astrocytes. Neuroscience 2009, 162, 328–338. [Google Scholar] [CrossRef]
- Kumar, D.K.; Choi, S.H.; Washicosky, K.J.; Eimer, W.A.; Tucker, S.; Ghofrani, J.; Lefkowitz, A.; McColl, G.; Goldstein, L.E.; Tanzi, R.E.; et al. Amyloid-β peptide protects against microbial infection in mouse and worm models of Alzheimer’s disease. Sci. Transl. Med. 2016, 8, 340ra72. [Google Scholar] [CrossRef] [PubMed]
- Ritchie, C.; Smailagic, N.; Noel-Storr, A.H.; Takwoingi, Y.; Flicker, L.; Mason, S.E.; McShane, R. Plasma and cerebrospinal fluid amyloid beta for the diagnosis of Alzheimer’s disease dementia and other dementias in people with mild cognitive impairment (MCI). Cochrane Database Syst. Rev. 2014, 2014, CD008782. [Google Scholar] [CrossRef]
- Carapeto, A.P.; Marcuello, C.; Faísca, P.F.N.; Rodrigues, M.S. Morphological and Biophysical Study of S100A9 Protein Fibrils by Atomic Force Microscopy Imaging and Nanomechanical Analysis. Biomolecules 2024, 14, 1091. [Google Scholar] [CrossRef]
- Xia, W.; Yang, T.; Shankar, G.; Smith, I.M.; Shen, Y.; Walsh, D.M.; Selkoe, D.J. A specific enzyme-linked immunosorbent assay for measuring beta-amyloid protein oligomers in human plasma and brain tissue of patients with Alzheimer disease. Arch. Neurol. 2009, 66, 190–199. [Google Scholar] [CrossRef]
- Olsson, B.; Lautner, R.; Andreasson, U.; Ohrfelt, A.; Portelius, E.; Bjerke, M.; Holtta, M.; Rosen, C.; Olsson, C.; Strobel, G.; et al. CSF and blood biomarkers for the diagnosis of Alzheimer’s disease: A systematic review and meta-analysis. Lancet Neurol. 2016, 15, 673–684. [Google Scholar] [CrossRef] [PubMed]
- Li, Q.X.; Evin, G.; Small, D.H.; Multhaup, G.; Beyreuther, K.; Masters, C.L. Proteolytic processing of Alzheimer’s disease beta A4 amyloid precursor protein in human platelets. J. Biol. Chem. 1995, 270, 14140–14147. [Google Scholar] [CrossRef]
- Citron, M.; Vigo-Pelfrey, C.; Teplow, D.B.; Miller, C.; Schenk, D.; Johnston, J.; Winblad, B.; Venizelos, N.; Lannfelt, L.; Selkoe, D.J. Excessive production of amyloid beta-protein by peripheral cells of symptomatic and presymptomatic patients carrying the Swedish familial Alzheimer disease mutation. Proc. Natl. Acad. Sci. USA 1994, 91, 11993–11997. [Google Scholar] [CrossRef]
- Kuo, Y.M.; Kokjohn, T.A.; Watson, M.D.; Woods, A.S.; Cotter, R.J.; Sue, L.I.; Kalback, W.M.; Emmerling, M.R.; Beach, T.G.; Roher, A.E. Elevated abeta42 in skeletal muscle of Alzheimer disease patients suggests peripheral alterations of AbetaPP metabolism. Am. J. Pathol. 2000, 156, 797–805. [Google Scholar] [CrossRef]
- Graff-Radford, N.R. Association of low plasma Aβ42/Aβ40 ratio with increased imminent risk for mild cognitive impairment and Alzheimer disease. Arch. Neurol. 2007, 64, 354–362. [Google Scholar] [CrossRef] [PubMed]
- Li, F.; Zhou, L.; Gao, X.; Ni, W.; Hu, J.; Wu, M.; Chen, S.; Han, J.; Wu, J. A Multichannel Fluorescent Tongue for Amyloid-β Aggregates Detection. Int. J. Mol. Sci. 2022, 23, 14562. [Google Scholar] [CrossRef] [PubMed]
- Sheikh, J.I.; Yesavage, J.A. Geriatric Depression Scale (GDS): Recent evidence and development of a shorter version. Clin. Gerontol. 1986, 5, 165–173. [Google Scholar]
- Katz, S.; Downs, T.D.; Cash, H.R.; Grotz, R.C. Progress in development of the index of ADL. Gerontologist 1970, 10, 20–30. [Google Scholar] [CrossRef]
- Lawton, M.P.; Brody, E.M. Assessment of older people: Self-maintaining and instrumental activities of daily living. Gerontologist 1969, 9, 179–186. [Google Scholar] [CrossRef]
- Folstein, M.F.; Folstein, S.E.; McHugh, P.R. Mini-mental state. A practical method for grading the cognitive state of patients for the clinician. J. Psychiatr. Res. 1975, 12, 189–198. [Google Scholar] [CrossRef]
- Dukelow, T.; Lawrence, E.G.; Jacobson, L.; Vassilev, P.; Koychev, I.; Muhammed, K.; Kennelly, S.P. Modifiable risk factors for dementia, and awareness of brain health behaviors: Results from the Five Lives Brain Health Ireland Survey (FLBHIS). Front. Psychol. 2023, 13, 1070259. [Google Scholar] [CrossRef] [PubMed]
- Livingston, G.; Huntley, J.; Liu, K.Y.; Costafreda, S.G.; Selbæk, G.; Alladi, S.; Alladi, S.; Ames, D.; Banerjee, S.; Burns, A.; et al. Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission. Lancet 2024, 404, 572–628. [Google Scholar] [CrossRef]
- Bouteloup, V.; Pellegrin, I.; Dubois, B.; Chene, G.; Planche, V.; Dufouil, C.; MEMENTO Study Group. Explaining the Variability of Alzheimer Disease Fluid Biomarker Concentrations in Memory Clinic Patients Without Dementia. Neurology 2024, 102, e209219. [Google Scholar] [CrossRef] [PubMed]
- Scheuner, D.; Eckman, C.; Jensen, M.; Song, X.; Citron, M.; Suzuki, N.; Bird, T.D.; Hardy, J.; Hutton, M.; Kukull, W.; et al. Secreted amyloid beta-protein similar to that in the senile plaques of Alzheimer’s disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer’s disease. Nat. Med. 1996, 2, 864–870. [Google Scholar] [CrossRef]
- Tamaoka, A.; Fukushima, T.; Sawamura, N.; Ishikawa, K.; Oguni, E.; Komatsuzaki, Y.; Shoji, S. Amyloid beta protein in plasma from patients with sporadic Alzheimer’s disease. J. Neurol. Sci. 1996, 141, 65–68. [Google Scholar] [CrossRef] [PubMed]
- Vanderstichele, H.; Van Kerschaver, E.; Hesse, C.; Davidsson, P.; Buyse, M.A.; Andreasen, N.; Minthon, L.; Wallin, A.; Blennow, K.; Vanmechelen, E. Standardization of measurement of beta-amyloid (1-42) in cerebrospinal fluid and plasma. Amyloid 2000, 7, 245–258. [Google Scholar] [CrossRef]
- Song, F.; Poljak, A.; Smythe, G.A.; Sachdev, P. Plasma biomarkers for mild cognitive impairment and Alzheimer’s disease. Brain Res. Rev. 2009, 61, 69–80. [Google Scholar] [CrossRef]
- Cammarata, S.; Borghi, R.; Giliberto, L.; Pardini, M.; Pollero, V.; Novello, C.; Fornaro, M.; Vitali, A.; Bracco, L.; Caltagirone, C.; et al. Amyloid-beta42 plasma levels are elevated in amnestic mild cognitive impairment. J. Alzheimers Dis. 2009, 18, 267–271. [Google Scholar] [CrossRef]
- Irizarry, M.C. Biomarkers of Alzheimer disease in plasma. NeuroRx 2004, 1, 226–234. [Google Scholar] [CrossRef]
- Mayeux, R.; Honig, L.S.; Tang, M.X.; Manly, J.; Stern, Y.; Schupf, N.; Mehta, P.D. Plasma A[beta]40 and A[beta]42 and Alzheimer’s disease: Relation to age, mortality, and risk. Neurology 2003, 61, 1185–1190. [Google Scholar] [CrossRef]
- Pomara, N.; Willoughby, L.M.; Sidtis, J.J.; Mehta, P.D. Selective reductions in plasma Abeta 1-42 in healthy elderly subjects during longitudinal follow-up: A preliminary report. Am. J. Geriatr. Psychiatry 2005, 13, 914–917. [Google Scholar]
- Hansson, O.; Zetterberg, H.; Vanmechelen, E.; Vanderstichele, H.; Andreasson, U.; Londos, E.; Wallin, A. Evaluation of plasma Abeta (40) and Abeta (42) as predictors of conversion to Alzheimer’s disease in patients with mild cognitive impairment. Neurobiol. Aging 2010, 31, 357–367. [Google Scholar] [CrossRef] [PubMed]
- Lopez, O.L.; Kuller, L.H.; Mehta, P.D.; Becker, J.T.; Gach, H.M.; Sweet, R.A.; Chang, Y.F.; Tracy, R.; DeKosky, S.T. Plasma amyloid levels and the risk of AD in normal subjects in the Cardiovascular Health Study. Neurology 2008, 70, 1664–1671. [Google Scholar] [CrossRef] [PubMed]
- Van Rossum, I.; Vos, S.; Handels, R.; Vissera, P.J. Biomarkers as Predictors for Conversion from Mild Cognitive Impairment to Alzheimer-Type Dementia: Implications for Trial Design. J. Alzheimers Dis. 2010, 20, 881–891. [Google Scholar] [CrossRef] [PubMed]
- Fei, M.; Jianghua, W.; Rujuan, M.; Wei, Z.; Qian, W. The relationship of plasma Aβ levels to dementia in aging individuals with mild cognitive impairment. J. Neurol. Sci. 2011, 305, 92–96. [Google Scholar] [CrossRef]
- Schupf, N.; Tang, M.X.; Fukuyama, H.; Manly, J.; Andrews, H.; Mehta, P.; Ravetch, J.; Mayeux, R. Peripheral Abeta subspecies as risk biomarkers of Alzheimer’s disease. Proc. Natl. Acad. Sci. USA 2008, 105, 14052–14057. [Google Scholar] [CrossRef]
- Janelidze, S.; Stomrud, E.; Palmqvist, S.; Zetterberg, H.; van Westen, D.; Jeromin, A.; Song, L.; Hanlon, D.; Tan Hehir, C.A.; Baker, D.; et al. Plasma β-amyloid in Alzheimer’s disease and vascular disease. Sci. Rep. 2016, 31, 26801. [Google Scholar] [CrossRef]
- Lövheim, H.; Elgh, F.; Johansson, A.; Zetterberg, H.; Blennow, K.; Hallmans, G.; Eriksson, S. Plasma concentrations of free amyloid-β cannot predict the development of Alzheimer’s disease. Alzheimers Dement. 2017, 13, 778–782. [Google Scholar] [CrossRef]
- Nakamura, A.; Kaneko, N.; Villemagne, V.L.; Kato, T.; Doecke, J.; Doré, V.; Fowler, C.; Li, Q.-X.; Martins, R.; Rowe, C.; et al. High performance plasma amyloid-β biomarkers for Alzheimer’s disease. Nature 2018, 554, 249–254. [Google Scholar] [CrossRef]
- Zetterberg, H.; Mörtberg, E.; Song, L.; Chang, L.; Provuncher, G.K.; Patel, P.P.; Ferrell, E.; Fournier, D.R.; Kan, C.W.; Campbell, T.G.; et al. Hypoxia due to cardiac arrest induces a time-dependent increase in serum amyloid β levels in humans. PLoS ONE 2011, 6, e28263. [Google Scholar] [CrossRef]
- Rembach, A.; Faux, N.G.; Watt, A.D.; Pertile, K.K.; Rumble, R.L.; Trounson, B.O.; Fowler, C.J.; Roberts, B.R.; Perez, K.A.; Li, Q.-X.; et al. Changes in plasma amyloid beta in a longitudinal study of aging and Alzheimer’s disease. Alzheimers Dement. 2014, 10, 53–61. [Google Scholar] [CrossRef] [PubMed]
- Rembach, A.; Watt, A.D.; Wilson, W.J.; Villemagne, V.L.; Burnham, S.C.; Ellis, K.A.; Maruff, P.; Ames, D.; Rowe, C.C.; Macaulay, S.L.; et al. Plasma amyloid-beta levels are significantly associated with a transition towards Alzheimer’s disease as measured by cognitive decline and change in neocortical amyloid burden. J. Alzheimers Dis. 2014, 40, 95–104. [Google Scholar] [CrossRef]
- Toledo, J.B.; Vanderstichele, H.; Figurski, M.; Aisen, P.S.; Petersen, R.C.; Weiner, M.W.; Jack, C.R.; Jagust, W.; Decarli, C.; Toga, A.W.; et al. Factors affecting Aβ plasma levels and their utility as biomarkers in ADNI. Acta Neuropathol. 2011, 122, 401–413. [Google Scholar] [CrossRef] [PubMed]
- Hardy, J.A.; Higgins, G.A. Alzheimer’s disease: The amyloid cascade hypothesis. Science 1992, 256, 184–185. [Google Scholar] [CrossRef]
- Kuo, Y.M.; Emmerling, M.R.; Lampert, H.C.; Hempelman, S.R.; Kokjohn, T.A.; Woods, A.S.; Cotter, R.J.; Roher, A.E. High levels of circulating Abeta42 are sequestered by plasma proteins in Alzheimer’s disease. Biochem. Biophys. Res. Commun. 1999, 257, 787–791. [Google Scholar] [CrossRef] [PubMed]
- Blennow, K.; Zetterberg, H. The Past and the Future of Alzheimer’s Disease Fluid Biomarkers. J. Alzheimers Dis. 2018, 62, 1125–1140. [Google Scholar] [CrossRef]
Cognitive Status | Cognitive Norm | MCI | Mild Dementia | Total | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Age | F | M | T | F | M | T | F | M | T | F | M | T |
66–74 | 13 | 13 | 26 | 17 | 14 | 31 | 7 | 13 | 20 | 37 | 40 | 77 |
75–85 | 12 | 15 | 27 | 11 | 15 | 26 | 12 | 14 | 26 | 35 | 44 | 79 |
85+ | 8 | 10 | 18 | 15 | 13 | 28 | 14 | 14 | 28 | 37 | 37 | 74 |
Total | 33 | 38 | 71 | 43 | 42 | 85 | 33 | 41 | 74 | 109 | 121 | 230 |
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McFarlane, O.; Kozakiewicz, M.; Kędziora-Kornatowska, K.; Gałęska-Śliwka, A.; Wojciechowska, M. Amyloid Beta as a Candidate Blood Biomarker of Early Cognitive Decline in the Elderly—A Preliminary Study. Curr. Issues Mol. Biol. 2025, 47, 203. https://doi.org/10.3390/cimb47030203
McFarlane O, Kozakiewicz M, Kędziora-Kornatowska K, Gałęska-Śliwka A, Wojciechowska M. Amyloid Beta as a Candidate Blood Biomarker of Early Cognitive Decline in the Elderly—A Preliminary Study. Current Issues in Molecular Biology. 2025; 47(3):203. https://doi.org/10.3390/cimb47030203
Chicago/Turabian StyleMcFarlane, Oliwia, Mariusz Kozakiewicz, Kornelia Kędziora-Kornatowska, Anita Gałęska-Śliwka, and Milena Wojciechowska. 2025. "Amyloid Beta as a Candidate Blood Biomarker of Early Cognitive Decline in the Elderly—A Preliminary Study" Current Issues in Molecular Biology 47, no. 3: 203. https://doi.org/10.3390/cimb47030203
APA StyleMcFarlane, O., Kozakiewicz, M., Kędziora-Kornatowska, K., Gałęska-Śliwka, A., & Wojciechowska, M. (2025). Amyloid Beta as a Candidate Blood Biomarker of Early Cognitive Decline in the Elderly—A Preliminary Study. Current Issues in Molecular Biology, 47(3), 203. https://doi.org/10.3390/cimb47030203