The N-Terminal Region of Amyloid β Controls the Aggregation Rate and Fibril Stability at Low pH through a Gain of Function Mechanism
Abstract
Alzheimer's disease is linked to a pathological polymerization of the endogenous amyloid β-peptide (Aβ) that ultimately forms amyloid plaques within the human brain. We used surface plasmon resonance (SPR) to measure the kinetic properties of Aβ fibril formation under different conditions during the polymerization process. For all polymerization processes, a critical concentration of free monomers, as defined by the dissociation equilibrium constant (K(D)), is required for the buildup of the polymer, for example, amyloid fibrils. At concentrations below the K(D), polymerization cannot occur. However, the K(D) for Aβ has previously been shown to be several orders of magnitude higher than the concentrations found in the cerebrospinal and interstitial fluids of the human brain, and the mechanism by which Aβ amyloid forms in vivo has been a matter of debate. Using SPR, we found that the K(D) of Aβ dramatically decreases as a result of lowering the pH. Importantly, this effect enables Aβ to polymerize within a picomolar concentration range that is close to the physiological Aβ concentration within the human brain. The stabilizing effect is dynamic, fully reversible, and notably pronounced within the pH range found within the endosomal and lysosomal pathways. Through sequential truncation, we show that the N-terminal region of Aβ contributes to the enhanced fibrillar stability due to a gain of function mechanism at low pH. Our results present a possible route for amyloid formation at very low Aβ concentrations and raise the question of whether amyloid formation in vivo is restricted to a low pH environment. These results have general implications for the development of therapeutic interventions.
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Aβ aggregation and accumulation start at the cellular level many years before the clinical diagnosis of Alzheimer's disease.
“However, the Aβ aggregation and accumulation start at the cellular level many years before the clinical diagnosis of AD (Morris et al., 1996; Brannstrom et al., 2014).”
From Exploring the Therapeutic Potential of Phytochemicals in Alzheimer’s Disease: Focus on Polyphenols and Monoterpenes (2022) · cites this paper as Brannstrom et al., 2014
Cites
NMRPipe: A multidimensional spectral processing system based on UNIX pipes
Delaglio, F., Grzesiek, S., Vuister, G. W., Zhu, G., Pfeifer, J., & Bax, A. (1995) · Journal of Biomolecular NMR · doi:10.1007/bf00197809 · Cited by 15,994 · see citing works
The Amyloid Hypothesis of Alzheimer’s Disease: Progress and Problems on the Road to Therapeutics
Hardy, J., & Selkoe, D. J. (2002) · Science · doi:10.1126/science.1072994 · Cited by 13,864 · see citing works
ExPASy: the proteomics server for in-depth protein knowledge and analysis
Gasteiger, E. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg563 · Cited by 5,602 · see citing works
The global prevalence of dementia: a systematic review and metaanalysis.
Prince, M., Bryce, R., Albanese, E., Wimo, A., Ribeiro, W., & Ferri, C. P. (2013) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2012.11.007 · Cited by 4,941 · see citing works
Amyloid plaque core protein in Alzheimer disease and Down syndrome.
Masters, C. L., Simms, G., Weinman, N. A., Multhaup, G., McDonald, B. L., & Beyreuther, K. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.12.4245 · Cited by 4,431 · see citing works
NMR View: A computer program for the visualization and analysis of NMR data
Johnson, B. A., & Blevins, R. A. (1994) · Journal of Biomolecular NMR · doi:10.1007/bf00404272 · Cited by 3,093 · see citing works
ACIDIFICATION OF THE ENDOCYTIC AND EXOCYTIC PATHWAYS
Mellman, I., Fuchs, R., & Helenius, A. (1986) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.55.070186.003311 · Cited by 2,010 · see citing works
Assembly and aggregation properties of synthetic Alzheimer's A4/beta amyloid peptide analogs.
Burdick, D., Soreghan, B., Kwon, M., Kosmoski, J., Knauer, M., Henschen, A., Yates, J., Cotman, C., & Glabe, C. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)48529-8 · Cited by 1,014 · see citing works
Intraneuronal Aβ42 Accumulation in Human Brain
Gouras, G. K., Tsai, J., Naslund, J., Vincent, B., Edgar, M., Checler, F., Greenfield, J. P., Haroutunian, V., Buxbaum, J. D., Xu, H., et al. (2000) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)64700-1 · Cited by 991 · see citing works
Distinct sites of intracellular production for Alzheimer's disease Aβ40/42 amyloid peptides
Hartmann, T., Bieger, S. C., Brühl, B., Tienari, P. J., Ida, N., Allsop, D., Roberts, G. W., Masters, C. L., Dotti, C. G., Unsicker, K., et al. (1997) · Nature Medicine · doi:10.1038/nm0997-1016 · Cited by 706 · see citing works
Bjellqvist, B., Basse, B., Olsen, E., & Celis, J. E. (1994) · Electrophoresis · doi:10.1002/elps.1150150171 · Cited by 559 · see citing works
The Oligomerization of Amyloid β-Protein Begins Intracellularly in Cells Derived from Human Brain
Walsh, D. M., Tseng, B. P., Rydel, R. E., Podlisny, M. B., & Selkoe, D. J. (2000) · Biochemistry · doi:10.1021/bi001048s · Cited by 502 · see citing works
Cook, D. G., Forman, M. S., Sung, J. C., Leight, S., Kolson, D. L., Iwatsubo, T., Lee, V. M.-Y., & Doms, R. W. (1997) · Nature Medicine · doi:10.1038/nm0997-1021 · Cited by 439 · see citing works
Amyloid seeds formed by cellular uptake, concentration, and aggregation of the amyloid-beta peptide
Hu, X., Crick, S. L., Bu, G., Frieden, C., Pappu, R. V., & Lee, J.-M. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0911281106 · Cited by 426 · see citing works
Qi-Takahara, Y., Morishima-Kawashima, M., Tanimura, Y., Dolios, G., Hirotani, N., Horikoshi, Y., Kametani, F., Maeda, M., Saido, T. C., Wang, R., et al. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.1575-04.2005 · Cited by 391 · see citing works
Treusch, S., Hamamichi, S., Goodman, J. L., Matlack, K. E. S., Chung, C. Y., Baru, V., Shulman, J. M., Parrado, A., Bevis, B. J., Valastyan, J. S., et al. (2011) · Science · doi:10.1126/science.1213210 · Cited by 379 · see citing works
Self-citationCataldo, A. M., Petanceska, S., Terio, N. B., Peterhoff, C. M., Durham, R., Mercken, M., Mehta, P. D., Buxbaum, J., Haroutunian, V., & Nixon, R. A. (2004) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2004.02.027 · Cited by 363 · see citing works
Alzheimer's Disease Amyloid Propagation by a Template-Dependent Dock-Lock Mechanism
Esler, W. P., Stimson, E. R., Jennings, J. M., Vinters, H. V., Ghilardi, J. R., Lee, J. P., Mantyh, P. W., & Maggio, J. E. (2000) · Biochemistry · doi:10.1021/bi992933h · Cited by 362 · see citing works
Haass, C., Hung, A. Y., Selkoe, D. J., & Teplow, D. B. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)32503-6 · Cited by 315 · see citing works
Pasternak, S., Bagshaw, R. D., Guiral, M., Zhang, S., Ackerley, C. A., Pak, B. J., Callahan, J. W., & Mahuran, D. J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m304009200 · Cited by 314 · see citing works
Intracellular Generation and Accumulation of Amyloid β-Peptide Terminating at Amino Acid 42
Wild-Bode, C., Yamazaki, T., Capell, A., Leimer, U., Steiner, H., Ihara, Y., & Haass, C. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.26.16085 · Cited by 303 · see citing works
Age- and region-dependent alterations in Aβ-degrading enzymes: implications for Aβ-induced disorders
Caccamo, A., Oddo, S., Sugarman, M. C., Akbari, Y., & LaFerla, F. M. (2005) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2004.06.013 · Cited by 299 · see citing works
Amyloid-β Dynamics Correlate with Neurological Status in the Injured Human Brain
Brody, D. L., Magnoni, S., Schwetye, K. E., Spinner, M. L., Esparza, T. J., Stocchetti, N., Zipfel, G. J., & Holtzman, D. M. (2008) · Science · doi:10.1126/science.1161591 · Cited by 295 · see citing works
Verdier, Y., Zarándi, M., & Penke, B. (2004) · Journal of Peptide Science · doi:10.1002/psc.573 · Cited by 261 · see citing works
Intraneuronal Aβ-Amyloid Precedes Development of Amyloid Plaques in Down Syndrome
Gyure, K. A., Durham, R., Stewart, W. F., Smialek, J. E., & Troncoso, J. C. (2001) · Archives of Pathology & Laboratory Medicine · doi:10.5858/2001-125-0489-iaapdo · Cited by 248 · see citing works
Regulation of endocytic pH by the Na+,K+-ATPase in living cells.
Cain, C. C., Sipe, D. M., & Murphy, R. F. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.2.544 · Cited by 234 · see citing works
Wertkin, A. M., Turner, R. S., Pleasure, S. J., Golde, T. E., Younkin, S. G., Trojanowski, J. Q., & Lee, V. M. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.20.9513 · Cited by 231 · see citing works
Kinetic analysis of beta-amyloid fibril elongation
Cannon, M. J., Williams, A. D., Wetzel, R. B., & Myszka, D. G. (2004) · Analytical Biochemistry · doi:10.1016/j.ab.2004.01.014 · Cited by 191 · see citing works
Li, J., Kanekiyo, T., Shinohara, M., Zhang, Y., LaDu, M. J., Xu, H., & Bu, G. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.420224 · Cited by 175 · see citing works
Xia, W., Zhang, J., Ostaszewski, B. L., Kimberly, W. T., Seubert, P. A., Koo, E. H., Shen, J., & Selkoe, D. J. (1998) · Biochemistry · doi:10.1021/bi9816195 · Cited by 169 · see citing works
Drew, S. C., Masters, C. L., & Barnham, K. J. (2009) · Journal of the American Chemical Society · doi:10.1021/ja903669a · Cited by 166 · see citing works
Tai, L. M., Bilousova, T., Jungbauer, L., Roeske, S. K., Youmans, K. L., Yu, C., Poon, W. W., Cornwell, L. B., Miller, C. A., Vinters, H. V., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.442103 · Cited by 165 · see citing works
Polymorph-Specific Kinetics and Thermodynamics of β-Amyloid Fibril Growth
Qiang, W., Kelley, K., & Tycko, R. (2013) · Journal of the American Chemical Society · doi:10.1021/ja311963f · Cited by 163 · see citing works
Turner, R. S., Suzuki, N., Chyung, A. S. C., Younkin, S. G., & Lee, V. M.-Y. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.15.8966 · Cited by 161 · see citing works
Annunziata, I., Patterson, A., Helton, D., Hu, H., Moshiach, S., Gomero, E., Nixon, R., & d’Azzo, A. (2013) · Nature Communications · doi:10.1038/ncomms3734 · Cited by 146 · see citing works
Evidence for intracellular cleavage of the Alzheimer's amyloid precursor in PC12 cells
Sambamurti, K., Shioi, J., Anderson, J. P., Pappolla, M. A., & Robakis, N. K. R. K. (1992) · Journal of Neuroscience Research · doi:10.1002/jnr.490330216 · Cited by 144 · see citing works
Acidic pH promotes the formation of toxic fibrils from β-amyloid peptide
Su, Y., & Chang, P.-T. (2001) · Brain Research · doi:10.1016/s0006-8993(00)03322-9 · Cited by 135 · see citing works
The Metalloprotease Meprin β Generates Amino Terminal-truncated Amyloid β Peptide Species
Bien, J., Jefferson, T., Čaušević, M., Jumpertz, T., Munter, L. M., Multhaup, G., Weggen, S., Becker‐Pauly, C., & Pietrzik, C. U. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.395608 · Cited by 131 · see citing works
Protein Interactions and Misfolding Analyzed by AFM Force Spectroscopy
McAllister, C., Karymov, M. A., Kawano, Y., Lushnikov, A. Y., Mikheikin, A., Uversky, V. N., & Lyubchenko, Y. L. (2005) · Journal of Molecular Biology · doi:10.1016/j.jmb.2005.10.012 · Cited by 126 · see citing works
Hasegawa, K., Ono, K., Yamada, M., & Naiki, H. (2002) · Biochemistry · doi:10.1021/bi020369w · Cited by 117 · see citing works
Martin, B. L., Schrader‐Fischer, G., Busciglio, J. A., Duke, M., Paganetti, P., & Yankner, B. A. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.45.26727 · Cited by 104 · see citing works
Winkler, E., Kamp, F., Scheuring, J., Ebke, A., Fukumori, A., & Steiner, H. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.356659 · Cited by 101 · see citing works
Elevated Plasma β-Amyloid Peptide Aβ42 Levels, Incident Dementia, and Mortality in Down Syndrome
Schupf, N., Patel, B. N., Pang, D. I., Zigman, W. B., Silverman, W. P., Mehta, P. D., & Mayeux, R. P. (2007) · Archives of Neurology · doi:10.1001/archneur.64.7.1007 · Cited by 100 · see citing works
Protective Effects of Positive Lysosomal Modulation in Alzheimer's Disease Transgenic Mouse Models
Butler, D., Hwang, J., Estick, C., Nishiyama, A., Kumar, S. S., Baveghems, C. L., Young-Oxendine, H. B., Wisniewski, M. L., Charalambides, A., & Bahr, B. A. (2011) · PLoS ONE · doi:10.1371/journal.pone.0020501 · Cited by 88 · see citing works
Probing solvent accessibility of amyloid fibrils by solution NMR spectroscopy
Ippel, H., Olofsson, A., Schleucher, J., Lundgren, E., & Wijmenga, S. S. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.132098999 · Cited by 87 · see citing works
Olofsson, A., Lindhagen‐Persson, M., Sauer-Eriksson, A. E., & Öhman, A. (2007) · Biochemical Journal · doi:10.1042/bj20061561 · Cited by 81 · see citing works
Evin, G. M., Cappai, R., Li, Q., Culvenor, J. G., Small, D. H., Beyreuther, K., & Masters, C. L. (1995) · Biochemistry · doi:10.1021/bi00043a024 · Cited by 78 · see citing works
Cerebrospinal Fluid Profiles of Amyloid β-Related Biomarkers in Alzheimer’s Disease
Rosén, C., Andréasson, U., Mattsson, N., Marcusson, J. O., Minthon, L., Andreasen, N., Blennow, K., & Zetterberg, H. (2012) · NeuroMolecular Medicine · doi:10.1007/s12017-012-8171-4 · Cited by 72 · see citing works
D’Andrea, M., & Nagele, R. (2010) · Biotechnic & Histochemistry · doi:10.3109/10520290903389445 · Cited by 66 · see citing works
Amyloid and Alzheimer's Disease: Inside and Out
Tam, J. H. K., & Pasternak, S. (2012) · Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · doi:10.1017/s0317167100013408 · Cited by 64 · see citing works
Kang, E. L., Biscaro, B., Piazza, F., & Tesco, G. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.407072 · Cited by 55 · see citing works
Aguilar, M. I., & Small, D. H. (2005) · Neurotoxicity Research · doi:10.1007/bf03033773 · Cited by 54 · see citing works
Structures of Oligomers of a Peptide from β-Amyloid
Pham, J. D., Chim, N., Goulding, C. W., & Nowick, J. S. (2013) · Journal of the American Chemical Society · doi:10.1021/ja4068854 · Cited by 53 · see citing works
Kulic, L., McAfoose, J., Welt, T., Tackenberg, C., Späni, C. B., Wirth, F., Finder, V. H., Konietzko, U., Giese, M., Eckert, A., et al. (2012) · Translational Psychiatry · doi:10.1038/tp.2012.109 · Cited by 51 · see citing works
Nicastrin is a resident lysosomal membrane protein
Bagshaw, R. D., Pasternak, S., Mahuran, D. J., & Callahan, J. W. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(02)02865-6 · Cited by 47 · see citing works
Effect of the surface charge of artificial model membranes on the aggregation of amyloid β-peptide
Sabaté, R., Espargaró, A., Barbosa‐Barros, L., Ventura, S., & Estelrich, J. (2012) · Biochimie · doi:10.1016/j.biochi.2012.03.027 · Cited by 46 · see citing works
Structural Biology of Presenilins and Signal Peptide Peptidases
Tomita, T., & Iwatsubo, T. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.r113.463281 · Cited by 45 · see citing works
Nagarathinam, A., Höflinger, P., Bühler, A., Schäfer, C., McGovern, G., Jeffrey, M., Staufenbiel, M., Jucker, M., & Baumann, F. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.2542-13.2013 · Cited by 44 · see citing works
Olofsson, A., Lindhagen‐Persson, M., Vestling, M., Sauer-Eriksson, A. E., & Öhman, A. (2009) · FEBS Journal · doi:10.1111/j.1742-4658.2009.07113.x · Cited by 41 · see citing works
Abramowski, D., Rabe, S., Upadhaya, A. R., Reichwald, J., Danner, S., Staab, D., Capetillo-Zarate, E., Yamaguchi, H., Saido, T. C., Wiederhold, K.-H., et al. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.4586-11.2012 · Cited by 41 · see citing works
Bustamante, H. A., Rivera-Dictter, A., Cavieres, V. A., Muñoz, V. C., González, A., Lin, Y., Mardones, G. A., & Burgos, P. V. (2013) · PLoS ONE · doi:10.1371/journal.pone.0083096 · Cited by 40 · see citing works
Increased Glutaminyl Cyclase Expression in Peripheral Blood of Alzheimer's Disease Patients
Valenti, M. T., Bolognin, S., Zanatta, C., Donatelli, L., Innamorati, G., Pampanin, M., Zanusso, G., Zatta, P. F., & Carbonare, L. D. (2013) · Journal of Alzheimer s Disease · doi:10.3233/jad-120517 · Cited by 38 · see citing works
Yuyama, K., & Yanagisawa, K. (2010) · Neuroscience Letters · doi:10.1016/j.neulet.2010.06.080 · Cited by 35 · see citing works
Intracellular Localization of Amyloid-β Peptide in SH-SY5Y Neuroblastoma Cells
Zheng, L. P., Calvo‐Garrido, J., Hallbeck, M., Hultenby, K. R., Marcusson, J. O., Cedazo-Mı́nguez, Á., & Terman, A. (2013) · Journal of Alzheimer s Disease · doi:10.3233/jad-122455 · Cited by 31 · see citing works
Lahiri, D. K., & Ge, Y. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1329.039 · Cited by 28 · see citing works
Ca2+ enhances Aβ polymerization rate and fibrillar stability in a dynamic manner
Brännström, K., Öhman, A., Lindhagen‐Persson, M., & Olofsson, A. (2012) · Biochemical Journal · doi:10.1042/bj20121583 · Cited by 26 · see citing works
Selectively 2H‐labeledGlu/Asp: application to pKa measurements in Aβ amyloid peptides
Zhang, S., & Lee, J. P. (2000) · Journal of Peptide Research · doi:10.1034/j.1399-3011.2000.00143.x · Cited by 19 · see citing works
Olofsson, A., Sauer-Eriksson, A. E., & Öhman, A. (2008) · Analytical Biochemistry · doi:10.1016/j.ab.2008.10.034 · Cited by 19 · see citing works
Aβ Peptide Fibrillar Architectures Controlled by Conformational Constraints of the Monomer
Brännström, K., Öhman, A., & Olofsson, A. (2011) · PLoS ONE · doi:10.1371/journal.pone.0025157 · Cited by 17 · see citing works
Hou, X., Small, D. H., & Aguilar, M. (2010) · Methods in molecular biology · doi:10.1007/978-1-60761-670-2_15 · Cited by 5 · see citing works
Myszka, D. G. (1999) · Journal of Molecular Recognition · doi:10.1002/(sici)1099-1352(199909/10)12:5
Flagged first, then by citations
1 of the 72 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
The Amyloid-β Pathway in Alzheimer’s Disease
Hampel, H., Hardy, J., Blennow, K., Chen, C., Perry, G., Kim, S. H., Villemagne, V. L., Aisen, P., Vendruscolo, M., Iwatsubo, T., et al. (2021) · Molecular Psychiatry · doi:10.1038/s41380-021-01249-0 · Cited by 1,952 · see citing works
Jeremic, D., Jiménez-Díaz, L., & Navarro-López, J. D. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101496 · Cited by 306 · see citing works
A short motif in the N-terminal region of α-synuclein is critical for both aggregation and function
Doherty, C. P. A., Ulamec, S. M., Maya‐Martinez, R., Good, S. C., Makepeace, J., Khan, G. N., van Oosten‐Hawle, P., Radford, S. E., & Brockwell, D. J. (2020) · Nature Structural & Molecular Biology · doi:10.1038/s41594-020-0384-x · Cited by 207 · see citing works
Effects of in vivo conditions on amyloid aggregation
Owen, M. C., Gnutt, D., Gao, M., Wärmländer, S. K. T. S., Jarvet, J., Gräslund, A., Winter, R., Ebbinghaus, S., & Strodel, B. (2019) · Chemical Society Reviews · doi:10.1039/c8cs00034d · Cited by 179 · see citing works
Critical aggregation concentration for the formation of early Amyloid-β (1–42) oligomers
Novo, M., Freire, S., & Al‐Soufi, W. (2018) · Scientific Reports · doi:10.1038/s41598-018-19961-3 · Cited by 174 · see citing works
Kehoe, P. G. (2018) · Journal of Alzheimer’s Disease · doi:10.3233/jad-171119 · Cited by 133 · see citing works
Ma, W., Yang, L., & He, L. (2018) · Journal of Pharmaceutical Analysis · doi:10.1016/j.jpha.2018.05.001 · Cited by 115 · see citing works
Advances in cell membrane chromatography
Ma, W., Wang, C., Liu, R., Wang, N., Lv, Y., Dai, B., & He, L. (2021) · Journal of Chromatography A · doi:10.1016/j.chroma.2021.461916 · Cited by 107 · see citing works
Stability matters, too – the thermodynamics of amyloid fibril formation
Buell, A. K. (2022) · Chemical Science · doi:10.1039/d1sc06782f · Cited by 98 · see citing works
The growth of amyloid fibrils: rates and mechanisms
Buell, A. K. (2019) · Biochemical Journal · doi:10.1042/bcj20160868 · Cited by 92 · see citing works
Amyloid‐beta 1‐40 is associated with alterations in NG2+ pericyte population ex vivo and in vitro
Schultz, N., Brännström, K., Byman, E., Moussaud, S., Nielsen, H. M., Bank, T. N. B., Olofsson, A., & Wennström, M. (2018) · Aging Cell · doi:10.1111/acel.12728 · Cited by 73 · see citing works
Piccialli, I., Tedeschi, V., Caputo, L., D’Errico, S., Ciccone, R., De Feo, V., Secondo, A., & Pannaccione, A. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.876614 · Cited by 73 · see citing works
Amylin alters human brain pericyte viability and NG2 expression
Schultz, N., Byman, E., Fex, M., & Wennström, M. (2016) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x16657093 · Cited by 69 · see citing works
Quantitative analysis of co-oligomer formation by amyloid-beta peptide isoforms.
Iljina, M., Garcia, G. A., Dear, A. J., Flint, J., Narayan, P., Michaels, T. C. T., Dobson, C. M., Frenkel, D., Knowles, T. P. J., & Klenerman, D. (2016) · Scientific Reports · doi:10.1038/srep28658 · Cited by 68 · see citing works
Ma, W., Yang, L., Lv, Y., Fu, J., Zhang, Y., & He, L. (2017) · Journal of Chromatography A · doi:10.1016/j.chroma.2017.04.053 · Cited by 64 · see citing works
Angiotensin-III is Increased in Alzheimer’s Disease in Association with Amyloid-β and Tau Pathology
Kehoe, P. G., Hibbs, E., Palmer, L. E., & Miners, J. S. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-161265 · Cited by 52 · see citing works
Dammers, C., Schwarten, M., Buell, A. K., & Willbold, D. (2017) · Chemical Science · doi:10.1039/c6sc04797a · Cited by 45 · see citing works
Jiang, Z., Dong, X., & Sun, Y. P. (2018) · Carbohydrate Research · doi:10.1016/j.carres.2018.03.001 · Cited by 46 · see citing works
The role of histidines in amyloid β fibril assembly
Brännström, K., Islam, T., Sandblad, L., & Olofsson, A. (2017) · FEBS Letters · doi:10.1002/1873-3468.12616 · Cited by 46 · see citing works
In vitro digestion and stability under environmental stresses of ovotransferrin nanofibrils
Wei, Z., & Huang, Q. (2019) · Food Hydrocolloids · doi:10.1016/j.foodhyd.2019.105343 · Cited by 41 · see citing works
Yang, J., Wang, X., Liu, J., Chi, W., Zhang, L., Xiao, L., & Yan, J. (2022) · Analytical Chemistry · doi:10.1021/acs.analchem.2c04042 · Cited by 35 · see citing works
Nilsson, L., Pamrén, A., Islam, T., Brännström, K., Surano, S., Pettersson, N., Iakovleva, I., Sandblad, L., Gharibyan, A. L., & Olofsson, A. (2018) · Journal of Molecular Biology · doi:10.1016/j.jmb.2018.06.005 · Cited by 30 · see citing works
Norrild, R. K., Vettore, N., Coden, A., Xue, W., & Buell, A. K. (2021) · Biophysical Chemistry · doi:10.1016/j.bpc.2021.106549 · Cited by 29 · see citing works
Multivariate effects of pH, salt, and Zn2+ ions on Aβ40 fibrillation
Wang, H., Wu, J., Sternke‐Hoffmann, R., Zheng, W., Mörman, C., & Luo, J. (2022) · Communications Chemistry · doi:10.1038/s42004-022-00786-1 · Cited by 28 · see citing works
Bhopatkar, A. A., & Kayed, R. (2023) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2023.105122 · Cited by 27 · see citing works
Ye, Z., Geng, X., Wei, L., Li, Z., Lin, S., & Xiao, L. (2020) · ACS Nano · doi:10.1021/acsnano.0c07555 · Cited by 28 · see citing works
The Amyloid Precursor Protein Shows a pH-Dependent Conformational Switch in Its E1 Domain
Hoefgen, S., Dahms, S. O., Oertwig, K., & Than, M. E. (2014) · Journal of Molecular Biology · doi:10.1016/j.jmb.2014.12.005 · Cited by 28 · see citing works
Au, D. F., Ostrovsky, D., Fu, R., & Vugmeyster, L. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.006559 · Cited by 28 · see citing works
Allosteric stabilization of the amyloid-β peptide hairpin by the fluctuating N-terminal
Xu, L., Nussinov, R., & Ma, B. (2015) · Chemical Communications · doi:10.1039/c5cc08107f · Cited by 26 · see citing works
The Properties of Amyloid-β Fibrils Are Determined by their Path of Formation
Brännström, K., Islam, T., Gharibyan, A. L., Iakovleva, I., Nilsson, L., Lee, C. C., Sandblad, L., Pamrén, A., & Olofsson, A. (2018) · Journal of Molecular Biology · doi:10.1016/j.jmb.2018.05.001 · Cited by 25 · see citing works
Pyroglutamate-Modified Amyloid-β(3–42) Shows α-Helical Intermediates before Amyloid Formation
Dammers, C., Reiß, K., Gremer, L., Lecher, J., Ziehm, T., Stoldt, M., Schwarten, M., & Willbold, D. (2017) · Biophysical Journal · doi:10.1016/j.bpj.2017.03.007 · Cited by 25 · see citing works
Residue‐Specific Dynamics and Local Environmental Changes in Aβ40 Oligomer and Fibril Formation
Liu, H., Morris, C., Lantz, R., Kent, T. W., Elbassal, E. A., Wojcikiewicz, E. P., & Du, D. (2018) · Angewandte Chemie International Edition · doi:10.1002/anie.201802490 · Cited by 22 · see citing works
Morris, C., Cupples, S., Kent, T. W., Elbassal, E. A., Wojcikiewicz, E. P., Peng, Y., & Du, D. (2018) · Chemistry - A European Journal · doi:10.1002/chem.201801805 · Cited by 22 · see citing works
Steady, Symmetric, and Reversible Growth and Dissolution of Individual Amyloid-β Fibrils
Xu, Y., Safari, M. S., Ma, W., Schafer, N. P., Wolynes, P. G., & Vekilov, P. G. (2019) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.9b00179 · Cited by 21 · see citing works
Recent developments in deuterium solid-state NMR for the detection of slow motions in proteins
Vugmeyster, L. (2021) · Solid State Nuclear Magnetic Resonance · doi:10.1016/j.ssnmr.2020.101710 · Cited by 21 · see citing works
Effect of Post-Translational Modifications and Mutations on Amyloid-β Fibrils Dynamics at N Terminus
Vugmeyster, L., Au, D. F., Ostrovsky, D., Kierl, B., Fu, R., Hu, Z., & Qiang, W. (2019) · Biophysical Journal · doi:10.1016/j.bpj.2019.09.004 · Cited by 20 · see citing works
Rivera-Marrero, S., Bencomo-Martínez, A., Salazar, E. O., Sablón-Carrazana, M., García-Pupo, L., Zoppolo, F., Arredondo, F., Dapueto, R., Santi, M. D., Kreimerman, I., et al. (2020) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2020.115700 · Cited by 20 · see citing works
von Einem, B., Wahler, A., Schips, T. G., Serrano‐Pozo, A., Proepper, C., Boeckers, T. M., Rueck, A. C., Wirth, T., Hyman, B. T., Danzer, K. M., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0129047 · Cited by 20 · see citing works
Li, L., Xu, S., Liu, L., Feng, R., Gong, Y., Zhao, X., Li, J., Cai, J., Feng, N., Wang, L., et al. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-160587 · Cited by 20 · see citing works
Apolipoprotein E impairs amyloid‐β fibril elongation and maturation
Islam, T., Gharibyan, A. L., Surano, S., Pettersson, N., Brännström, K., Hedberg, I., Virta, M., Olofsson, L., & Olofsson, A. (2019) · FEBS Journal · doi:10.1111/febs.15075 · Cited by 20 · see citing works
A Potential Role for α-Amylase in Amyloid-β-Induced Astrocytic Glycogenolysis and Activation
Byman, E., Bank, T. N. B., Schultz, N., Blom, A. M., & Wennström, M. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-180997 · Cited by 17 · see citing works
Vugmeyster, L., Au, D. F., Ostrovsky, D., & Fu, R. (2019) · ChemPhysChem · doi:10.1002/cphc.201900363 · Cited by 16 · see citing works
Zhao, W., & Ai, H. (2018) · ChemPhysChem · doi:10.1002/cphc.201701384 · Cited by 15 · see citing works
Zimbone, S., Giuffrida, M. L., Sabatino, G., Natale, G. D., Tosto, R., Consoli, G. M. L., Milardi, D., Pappalardo, G., & Sciacca, M. F. M. (2023) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.2c00720 · Cited by 15 · see citing works
Inhibition of Amyloid β Aggregation and Cytotoxicity by Berbamine Hydrochloride
Dong, L., Xie, H., Jia, L., Hong, L., & Gao, L. (2023) · Chemistry - A European Journal · doi:10.1002/chem.202301865 · Cited by 14 · see citing works
Structural Insights into Seeding Mechanisms of hIAPP Fibril Formation
Suladze, S., Martinez, C. S., Camargo, D. C. R., Engler, J., Rodina, N. P., Sarkar, R., Zacharias, M., & Reif, B. (2024) · Journal of the American Chemical Society · doi:10.1021/jacs.3c14233 · Cited by 14 · see citing works
Byman, E., Martinsson, I., Haukedal, H., Bank, T. N. B., Gouras, G. K., Freude, K., & Wennström, M. (2021) · Aging Cell · doi:10.1111/acel.13433 · Cited by 14 · see citing works
Single-molecule probing of amyloid nano-ensembles using the polymer nanoarray approach
Maity, S., Viazovkina, E., Gall, A. A., & Lyubchenko, Y. L. (2017) · Physical Chemistry Chemical Physics · doi:10.1039/c7cp02691a · Cited by 13 · see citing works
Microglial Lyzl4 Facilitates β‐Amyloid Clearance in Alzheimer's Disease
Pan, J., Zhong, J., Geng, J., Oberhauser, J., Shi, S., & Wan, J. (2024) · Advanced Science · doi:10.1002/advs.202412184 · Cited by 11 · see citing works
Deuteron rotating frame relaxation for the detection of slow motions in rotating solids
Vugmeyster, L., Ostrovsky, D., Greenwood, A. I., & Fu, R. (2022) · Journal of Magnetic Resonance · doi:10.1016/j.jmr.2022.107171 · Cited by 11 · see citing works
Nuñez‐Diaz, C., Pocevičiūtė, D., Schultz, N., Bank, T. N. B., Welinder, C., Swärd, K., & Wennström, M. (2023) · Molecular Brain · doi:10.1186/s13041-023-01013-1 · Cited by 10 · see citing works
Miao, Y., Tang, X. L., & Han, W. (2022) · Chemical Science · doi:10.1039/d1sc06337e · Cited by 9 · see citing works
Aggarwal, L., & Biswas, P. (2020) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.9b10425 · Cited by 9 · see citing works
Brännström, K., Gharibyan, A. L., Islam, T., Iakovleva, I., Nilsson, L., Lee, C. C., Sandblad, L., Pamrén, A., & Olofsson, A. (2018) · Data in Brief · doi:10.1016/j.dib.2018.05.129 · Cited by 9 · see citing works
Bai, S., Wang, Y., Ye, W.-L., Wu, S.-Y., Jia, L., Hong, L., Xie, H., & Gao, L. (2025) · Communications Chemistry · doi:10.1038/s42004-025-01587-y · Cited by 8 · see citing works
Xu, W. W., Mei, J., Wang, C., Yang, H., Ma, X., Gao, W., Ahmad, S., & Ai, H. (2023) · Physical Chemistry Chemical Physics · doi:10.1039/d3cp01683h · Cited by 7 · see citing works
Guan, Y., Li, Y., Gao, W., Mei, J., Xu, W. W., Wang, C., & Ai, H. (2023) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.3c00585 · Cited by 7 · see citing works
Sodium Oligomannate Electrostatically Binds to Aβ and Blocks Its Aggregation
Zhou, C., Zhang, J., Luo, X., Lian, F., Zeng, Y., Zhang, Z., Zhang, H., & Zhang, N. (2023) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.3c00280 · Cited by 6 · see citing works
Islam, T., Gharibyan, A. L., Lee, C. C., & Olofsson, A. (2019) · BMC Biotechnology · doi:10.1186/s12896-019-0589-4 · Cited by 6 · see citing works
Effects of the Hydrophilic N-Terminal Region on Aβ-Mediated Membrane Disruption
Morris, C., Kent, T. W., Shen, F., Wojcikiewicz, E. P., & Du, D. (2021) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.1c03413 · Cited by 5 · see citing works
Lemos, R., Pérez‐Badell, Y., Nisco, M. D., Carpentieri, A., Suárez, M., & Pedatella, S. (2024) · ChemPlusChem · doi:10.1002/cplu.202400404 · Cited by 5 · see citing works
Young, K. A., & Mancera, R. L. (2022) · Analytical Biochemistry · doi:10.1016/j.ab.2022.114828 · Cited by 5 · see citing works
Vugmeyster, L., & Ostrovsky, D. (2020) · Magnetic Resonance in Chemistry · doi:10.1002/mrc.5114 · Cited by 4 · see citing works
Vugmeyster, L., Au, D. F., Ostrovsky, D., Rickertsen, D. R. L., & Reed, S. M. (2020) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.0c02490 · Cited by 3 · see citing works
Metals and amyloid gain-of-toxic mechanisms in neurodegenerative diseases
Cristóvão, J. S., Moreira, G. G., Grabrucker, A. M., & Gomes, C. M. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-819132-3.00009-9 · Cited by 3 · see citing works
Gao, X., Zhai, J., He, X., Ding, W., & Shen, B. (2024) · TrAC Trends in Analytical Chemistry · doi:10.1016/j.trac.2024.117623 · Cited by 2 · see citing works
Helices with Rational Residues Conduct Different Modulations towards Aβ Aggregation
Zhang, Z.-X., Hu, Z., Zhao, D.-S., Chen, Y., & Li, Y. (2017) · Chemistry Letters · doi:10.1246/cl.170229 · Cited by 2 · see citing works
Zhao, W., Xing, X., Kang, B., Zhu, X., & Ai, H. (2018) · Journal of Molecular Graphics and Modelling · doi:10.1016/j.jmgm.2018.04.003 · Cited by 2 · see citing works
Zein, H. F. (2026) · Chemical Physics · doi:10.1016/j.chemphys.2026.113284 · Cited by 1 · see citing works
Residue‐Specific Dynamics and Local Environmental Changes in Aβ40 Oligomer and Fibril Formation
Liu, H., Morris, C., Lantz, R., Kent, T. W., Elbassal, E. A., Wojcikiewicz, E. P., & Du, D. (2018) · Angewandte Chemie · doi:10.1002/ange.201802490 · Cited by 1 · see citing works
Mirkin, N. G., & Krimm, S. (2018) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.8b00612 · Cited by 1 · see citing works
Amyloid-β aggregates induced by β-cholesteryl glucose-embedded liposomes.
Shimanouchi, T., Sano, Y., Yasuhara, K., & Kimura, Y. (2022) · Biochimica et Biophysica Acta - Proteins and Proteomics · doi:10.1016/j.bbapap.2022.140816 · Cited by 1 · see citing works
Feng, L. (2019) · Research Online (University of Wollongong)
Feng, L., Watanabe, H., Molino, P. J., Wallace, G. G., Phung, S. L., Uchihashi, T., & Higgins, M. J. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.10.17.343830
- Authors
- Brännström, K., Öhman, A., Nilsson, L., Pihl, M., Sandblad, L., & Olofsson, A.
- Affiliations
- Umeå University (SE)
- Corresponding author
- Olofsson, Anders
- Venue
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Published
- 2014-07-28
- Volume
- 136
- Issue
- 31
- Pages
- 10956-10964
- ISSN
- 0002-7863 (ISSN-L)
- 1520-5126
- OpenAlex
- W2041383508
- Cited by
- 74
- References
- 72
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 4 · 2023: 7 · 2022: 8 · 2021: 7 · 2020: 8 · 2019: 11 · 2018: 14 · 2017: 8 · 2016: 2 · 2015: 2 · 2014: 1
- FWCI
- 2.85
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of the American Chemical Society (publishedVersion)
- PubMed (publishedVersion)
- Funders
- V?sterbotten L?ns Landsting
- Vetenskapsr?det
- Erling-Persson Family Foundation
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
- Keywords
- amyloid-beta, N-terminal domain, amyloid fibril formation, aggregation kinetics, fibril stability, gain-of-function, dissociation equilibrium constant, Alzheimer's disease, amyloid plaques
- MeSH terms
- Hydrogen-Ion Concentration, Kinetics, Peptide Fragments, Amyloid beta-Peptides, Protein Structure, Secondary, Protein Multimerization, Protein Stability, Protein Aggregates
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