Publications

Recent Publications

Rodriguez G, Eren M, Haupfear I, Viola KL, Cline EN, Miyata T, Klein WL, Vaughan DE, Dong H. Pharmacological inhibition of plasminogen activator inhibitor-1 prevents memory deficits and reduces neuropathology in APP/PS1 mice. Psychopharmacology (Berl). 2023 Dec;240(12):2641-2655. doi: 10.1007/s00213-023-06459-8.

Kandi S, Cline EN, Rivera BM, Viola KL, Zhu J, Condello C, LeDuc RD, Klein WL, Kelleher NL, Patrie SM. Amyloid β Proteoforms Elucidated by Quantitative LC/MS in the 5xFAD Mouse Model of Alzheimer’s Disease. J Proteome Res. 2023 Nov 3;22(11):3475-3488. doi: 10.1021/acs.jproteome.3c00353.

Selles MC, Fortuna JTS, Cercato MC, Santos LE, Domett L, Bitencourt ALB, Carraro MF, Souza AS, Janickova H, Azevedo CV, Campos HC, de Souza JM, Alves- Leon S, Prado VF, Prado MAM, Epstein AL, Salvetti A, Longo BM, Arancio O, Klein WL, Sebollela A, De Felice FG, Jerusalinsky DA, Ferreira ST. AAV-mediated neuronal expression of an scFv antibody selective for Aβ oligomers protects synapses and rescues memory in Alzheimer models. Mol Ther. 2023 Feb 1;31(2):409-419. doi: 10.1016/j.ymthe.2022.11.002.

Klein WL. A time for optimism in the dementia field. Front Dement. 2022 Oct 18;1:1038003. doi: 10.3389/frdem.2022.1038003.

Wakeman DR, Weed MR, Perez SE, Cline EN, Viola KL, Wilcox KC, Moddrelle DS, Nisbett EZ, Kurian AM, Bell AF, Pike R, Jacobson PB, Klein WL, Mufson EJ, Lawrence MS, Elsworth JD. Intrathecal amyloid-beta oligomer administration increases tau phosphorylation in the medial temporal lobe in the African green monkey: A nonhuman primate model of Alzheimer’s disease. Neuropathol Appl Neurobiol. 2022 Jun;48(4):e12800. doi: 10.1111/nan.12800.

Bartley SC, Proctor MT, Xia H, Ho E, Kang DS, Schuster K, Bicca MA, Seckler HS, Viola KL, Patrie SM, Kelleher NL, De Mello FG, Klein WL. An Essential Role for Alzheimer’s-Linked Amyloid Beta Oligomers in Neurodevelopment: Transient Expression of Multiple Proteoforms during Retina Histogenesis. Int J Mol Sci. 2022 Feb 17;23(4):2208. doi: 10.3390/ijms23042208.

Weiss C, Bertolino N, Procissi D, Aleppo G, Smith QC, Viola KL, Bartley SC, Klein WL, Disterhoft JF. Diet-induced Alzheimer’s-like syndrome in the rabbit. Alzheimers Dement (N Y). 2022 Feb 1;8(1):e12241. doi: 10.1002/trc2.12241.

Yang Y, Tapias V, Acosta D, Xu H, Chen H, Bhawal R, Anderson ET, Ivanova E, Lin H, Sagdullaev BT, Chen J, Klein WL, Viola KL, Gandy S, Haroutunian V, Beal MF, Eliezer D, Zhang S, Gibson GE. Altered succinylation of mitochondrial proteins, APP and tau in Alzheimer’s disease. Nat Commun. 2022 Jan 10;13(1):159. doi: 10.1038/s41467-021-27572-2.

Viola KL, Bicca MA, Bebenek AM, Kranz DL, Nandwana V, Waters EA, Haney CR, Lee M, Gupta A, Brahmbhatt Z, Huang W, Chang TT, Peck A, Valdez C, Dravid VP, Klein WL. The Therapeutic and Diagnostic Potential of Amyloid β Oligomers Selective Antibodies to Treat Alzheimer’s Disease. Front Neurosci. 2022 Jan 3;15:768646. doi: 10.3389/fnins.2021.768646.

Suong DNA, Imamura K, Inoue I, Kabai R, Sakamoto S, Okumura T, Kato Y, Kondo T, Yada Y, Klein WL, Watanabe A, Inoue H. Induction of inverted morphology in brain organoids by vertical-mixing bioreactors. Commun Biol. 2021 Oct 22;4(1):1213. doi: 10.1038/s42003-021-02719-5.

Kelly L, Seifi M, Ma R, Mitchell SJ, Rudolph U, Viola KL, Klein WL, Lambert JJ, Swinny JD. Identification of intraneuronal amyloid beta oligomers in locus coeruleus neurons of Alzheimer’s patients and their potential impact on inhibitory neurotransmitter receptors and neuronal excitability. Neuropathol Appl Neurobiol. 2021 Jun;47(4):488-505. doi: 10.1111/nan.12674.

Bitencourt ALB, Campos RM, Cline EN, Klein WL, Sebollela A. Antibody Fragments as Tools for Elucidating Structure-Toxicity Relationships and for Diagnostic/Therapeutic Targeting of Neurotoxic Amyloid Oligomers. Int J Mol Sci. 2020 Nov 24;21(23):8920. doi: 10.3390/ijms21238920.

Rozema NB, Procissi D, Bertolino N, Viola KL, Nandwana V, Abdul N, Pribus S, Dravid V, Klein WL, Disterhoft JF, Weiss C. Aβ oligomer induced cognitive impairment and evaluation of ACU193-MNS-based MRI in rabbit. Alzheimers Dement (N Y). 2020 Oct 10;6(1):e12087. doi: 10.1002/trc2.12087. Erratum in: Alzheimers Dement (N Y). 2021 Apr 09;7(1):1. doi: 10.1002/trc2.12165.

Welikovitch LA, Do Carmo S, Maglóczky Z, Malcolm JC, Lőke J, Klein WL, Freund T, Cuello AC. Early intraneuronal amyloid triggers neuron-derived inflammatory signaling in APP transgenic rats and human brain. Proc Natl Acad Sci U S A. 2020 Mar 24;117(12):6844-6854. doi: 10.1073/pnas.1914593117.

Ding Y, Zhao J, Zhang X, Wang S, Viola KL, Chow FE, Zhang Y, Lippa C, Klein WL, Gong Y. Amyloid Beta Oligomers Target to Extracellular and Intracellular Neuronal Synaptic Proteins in Alzheimer’s Disease. Front Neurol. 2019 Nov 1;10:1140. doi: 10.3389/fneur.2019.01140.

Xie Z, Shapiro LP, Cahill ME, Russell TA, Lacor PN, Klein WL, Penzes P. Kalirin-7 prevents dendritic spine dysgenesis induced by amyloid beta-derived oligomers. Eur J Neurosci. 2019 May;49(9):1091-1101. doi: 10.1111/ejn.14311.

Cline EN, Das A, Bicca MA, Mohammad SN, Schachner LF, Kamel JM, DiNunno N, Weng A, Paschall JD, Bu RL, Khan FM, Rollins MG, Ives AN, Shekhawat G, Nunes- Tavares N, de Mello FG, Compton PD, Kelleher NL, Klein WL. A novel crosslinking protocol stabilizes amyloid β oligomers capable of inducing Alzheimer’s-associated pathologies. J Neurochem. 2019 Mar;148(6):822-836. doi: 10.1111/jnc.14647.

Mendes ND, Fernandes A, Almeida GM, Santos LE, Selles MC, Lyra E Silva NM, Machado CM, Horta-Júnior JAC, Louzada PR, De Felice FG, Alves-Leon S, Marcondes J, Assirati JA Jr, Matias CM, Klein WL, Garcia-Cairasco N, Ferreira ST, Neder L, Sebollela A. Free-floating adult human brain-derived slice cultures as a model to study the neuronal impact of Alzheimer’s disease-associated Aβ oligomers. J Neurosci Methods. 2018 Sep 1;307:203-209. doi: 10.1016/j.jneumeth.2018.05.021.

Batista AF, Forny-Germano L, Clarke JR, Lyra E Silva NM, Brito-Moreira J, Boehnke SE, Winterborn A, Coe BC, Lablans A, Vital JF, Marques SA, Martinez AM, Gralle M, Holscher C, Klein WL, Houzel JC, Ferreira ST, Munoz DP, De Felice FG. The diabetes drug liraglutide reverses cognitive impairment in mice and attenuates insulin receptor and synaptic pathology in a non-human primate model of Alzheimer’s disease. J Pathol. 2018 May;245(1):85-100. doi: 10.1002/path.5056.

Yin J, Zhao F, Chojnacki JE, Fulp J, Klein WL, Zhang S, Zhu X. NLRP3 Inflammasome Inhibitor Ameliorates Amyloid Pathology in a Mouse Model of Alzheimer’s Disease. Mol Neurobiol. 2018 Mar;55(3):1977-1987. doi: 10.1007/s12035-017-0467-9.

Cline EN, Bicca MA, Viola KL, Klein WL. (2018). The Amyloid-β Oligomer Hypothesis: Beginning of the Third Decade. J Alzheimers Dis. 64(s1):S567-S610. doi: 10.3233/JAD-179941.

Pitt J, Wilcox KC, Tortelli V, Diniz LP, Oliveira MS, Dobbins C, Yu XW, Nandamuri S, Gomes FCA, DiNunno N, Viola KL, De Felice FG, Ferreira ST, Klein WL. (2017). Neuroprotective astrocyte-derived insulin/insulin-like growth factor 1 stimulates endocytic processing and extracellular release of neuron-bound Aβ oligomers. Mol Biol Cell. 28(20):2623-2636. doi: 10.1091/mbc.E17-06-0416.

DiChiara T, DiNunno N, Clark J, Bu RL, Cline EN, Rollins MG, Gong Y, Brody DL, Sligar SG, Velasco PT, Viola KL, Klein WL. (2017). Alzheimer’s Toxic Amyloid Beta Oligomers: Unwelcome Visitors to the Na/K ATPase alpha3 Docking Station. Yale J Biol Med. 90(1):45-61.

Knight EM, Kim SH, Kottwitz JC, Hatami A, Albay R, Suzuki A, Lublin A, Alberini CM, Klein WL, Szabo P, Relkin NR, Ehrlich M, Glabe CG, Gandy S, Steele JW. (2016). Effective anti-Alzheimer Aβ therapy involves depletion of specific Aβ oligomer subtypes. Neurol Neuroimmunol Neuroinflamm. 3(3):e237. doi: 10.1212/NXI.0000000000000237.

Viola KL, Sbarboro J, Sureka R, De M, Bicca MA, Wang J, Vasavada S, Satpathy S, Wu S, Joshi H, Velasco PT, MacRenaris K, Waters EA, Lu C, Phan J, Lacor P, Prasad P, Dravid VP, Klein WL. (2015). Towards non-invasive diagnostic imaging of early-stage Alzheimer’s disease. Nat Nanotechnol. 10(1):91-8. doi: 10.1038/nnano.2014.254.

Viola KL, Klein WL. (2015) Amyloid β oligomers in Alzheimer’s disease pathogenesis, treatment, and diagnosis. Acta Neuropathol. 129(2):183-206. doi: 10.1007/s00401-015-1386-3.

Wilcox KC, Marunde MR, Das A, Velasco PT, Kuhns BD, Marty MT, Jiang H, Luan CH, Sligar SG, Klein WL. (2015). Nanoscale Synaptic Membrane Mimetic Allows Unbiased High Throughput Screen That Targets Binding Sites for Alzheimer’s-Associated Aβ Oligomers. PLoS One. 10(4):e0125263. doi: 10.1371/journal.pone.0125263.

Forny-Germano L, Lyra e Silva NM, Batista AF, Brito-Moreira J, Gralle M, Boehnke SE, Coe BC, Lablans A, Marques SA, Martinez AM, Klein WL, Houzel JC, Ferreira ST, Munoz DP, De Felice FG. (2014). Alzheimer’s disease-like pathology induced by amyloid-β oligomers in nonhuman primates. J Neurosci. 34(41):13629-43. doi: 10.1523/JNEUROSCI.1353-14.2014.

WL Klein. (2014). Targeting Aß oligomers: a molecular basis for the cause, diagnosis, and treatment of Alzheimer’s disease. Henry Stewart Talks – The Biomedical & Life Sciences Collection. hstalks.com

Lourenco MV, Clarke JR, Frozza RL, Bomfim TR, Forny-Germano L, Batista AF, Sathler LB, Brito-Moreira J, Amaral OB, Silva CA, Freitas-Correa L, Espírito-Santo S, Campello-Costa P, Houzel JC, Klein WL, Holscher C, Carvalheira JB, Silva AM, Velloso LA, Munoz DP, Ferreira ST, De Felice FG. (2013). TNF-α mediates PKR-dependent memory impairment and brain IRS-1 inhibition induced by Alzheimer’s β-amyloid oligomers in mice and monkeys. Cell Metab. 18(6):831-43. doi: 10.1016/j.cmet.2013.11.002.

Kondo T, Asai M, Tsukita K, Kutoku Y, Ohsawa Y, Sunada Y, Imamura K, Egawa N, Yahata N, Okita K, Takahashi K, Asaka I, Aoi T, Watanabe A, Watanabe K, Kadoya C, Nakano R, Watanabe D, Maruyama K, Hori O, Hibino S, Choshi T, Nakahata T, Hioki H, Kaneko T, Naitoh M, Yoshikawa K, Yamawaki S, Suzuki S, Hata R, Ueno S, Seki T, Kobayashi K, Toda T, Murakami K, Irie K, Klein WL, Mori H, Asada T, Takahashi R, Iwata N, Yamanaka S, Inoue H. (2013). Modeling Alzheimer’s disease with iPSCs reveals stress phenotypes associated with intracellular Aβ and differential drug responsiveness. Cell Stem Cell. 12(4):487-96. doi: 10.1016/j.stem.2013.01.009.

Bomfim TR, Forny-Germano L, Sathler LB, Brito-Moreira J, Houzel JC, Decker H, Silverman MA, Kazi H, Melo HM, McClean PL, Holscher C, Arnold SE, Talbot K, Klein WL, Munoz DP, Ferreira ST, De Felice FG. (2012). An anti-diabetes agent protects the mouse brain from defective insulin signaling caused by Alzheimer’s disease- associated Aβ oligomers. J Clin Invest,122(4):1339-53.

Ferreira ST, Klein WL. (2011). The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer’s disease. Neurobiol Learn Mem, 96(4):529-43.

Renner M, Lacor PN, Velasco PT, Xu J, Contractor A, Klein WL, Triller A. (2010). Deleterious effects of amyloid β oligomers acting as an extracellular scaffold for mGluR5. Neuron, 66(5):739-54.

Tomiyama T, Matsuyama S, Iso H, Umeda T, Takuma H, Ohnishi K, Ishibashi K, Teraoka R, Sakama N, Yamashita T, Nishitsuji K, Ito K, Shimada H, Lambert MP, Klein WL, Mori H. (2010). A mouse model of amyloid β oligomers: their contribution to synaptic alteration, abnormal tau phosphorylation, glial activation, and neuronal loss in vivo. J Neurosci, 30(14):4845-56.

De Felice FG, Vieira MN, Bomfim TR, Decker H, Velasco PT, Lambert MP, Viola KL, Zhao WQ, Ferreira ST, Klein WL. (2009). Protection of synapses against Alzheimer’s-linked toxins: insulin signaling prevents the pathogenic binding of Aβ oligomers. Proc Natl Acad Sci U S A,106(6):1971-6.

Lacor PN, Buniel MC, Furlow PW, Clemente AS, Velasco PT, Wood M, Viola KL, Klein WL. (2007). Aβ oligomer-induced aberrations in synapse composition, shape, and density provide a molecular basis for loss of connectivity in Alzheimer’s disease. J Neurosci, 27(4):796-807.

De Felice FG, Velasco PT, Lambert MP, Viola K, Fernandez SJ, Ferreira ST, Klein WL. (2007). Aβ oligomers induce neuronal oxidative stress through an N-methyl-D-aspartate receptor-dependent mechanism that is blocked by the Alzheimer drug memantine. J Biol Chem, 282(15):11590-601.

Lambert MP, Velasco PT, Chang L, Viola KL, Fernandez S, Lacor PN, Khuon D, Gong Y, Bigio EH, Shaw P, De Felice FG, Krafft GA, Klein WL. (2007). Monoclonal antibodies that target pathological assemblies of Abeta. J Neurochem. 100(1):23-35.

Georganopoulou DG, Chang L, Nam JM, Thaxton CS, Mufson EJ, Klein WL, Mirkin CA. (2005). Nanoparticle-based detection in cerebral spinal fluid of a soluble pathogenic biomarker for Alzheimer’s disease. Proc Natl Acad Sci U S A,102(7):2273-6.

Haes AJ, Chang L, Klein WL, Van Duyne RP. (2005). Detection of a biomarker for Alzheimer’s disease from synthetic and clinical samples using a nanoscale optical biosensor. J Am Chem Soc. 127(7):2264-71.

Lacor PN, Buniel MC, Chang L, Fernandez SJ, Gong Y, Viola KL, Lambert MP, Velasco PT, Bigio EH, Finch CE, Krafft GA, Klein WL. (2004) Synaptic targeting by Alzheimer’s-related amyloid β oligomers. J Neurosci, 24(45):10191-200.

Gong Y, Chang L, Viola KL, Lacor PN, Lambert MP, Finch CE, Krafft GA, Klein WL. (2003). Alzheimer’s disease-affected brain: presence of oligomeric Aβ ligands (ADDLs) suggests a molecular basis for reversible memory loss. Proc Natl Acad Sci U S A, (18):10417-22.

Chromy BA, Nowak RJ, Lambert MP, Viola KL, Chang L, Velasco PT, Jones BW, Fernandez SJ, Lacor PN, Horowitz P, Finch CE, Krafft GA, Klein WL. (2003). Self-assembly of Abeta(1-42) into globular neurotoxins. Biochemistry. 42(44):12749-60.

Klein WL, Krafft GA, Finch CE. (2001). Targeting small Abeta oligomers: the solution to an Alzheimer’s disease conundrum? Trends Neurosci. 24(4):219-24.

Lambert MP, Barlow AK, Chromy BA, Edwards C, Freed R, Liosatos M, Morgan TE, Rozovsky I, Trommer B, Viola KL, Wals P, Zhang C, Finch CE, Krafft GA, Klein WL. (1998). Diffusible, nonfibrillar ligands derived from Aβ1-42 are potent central nervous system neurotoxins. Proc Natl Acad Sci U S A, 95(11):6448-53.

Milestone Publications

Introduction of the AβO hypothesis for AD.
Lambert MP, Barlow AK, Chromy BA, Edwards C, Freed R, Liosatos M, Morgan TE, Rozovsky I, Trommer B, Viola KL, Wals P, Zhang C, Finch CE, Krafft GA, Klein WL. (1998). Diffusible, nonfibrillar ligands derived from Aβ1-42 are potent central nervous system neurotoxins. Proc Natl Acad Sci U S A, 95(11):6448-53.

Discovery that AβOs impair mechanisms of memory, inhibiting LTP and promoting LTD.
Lambert MP, Barlow AK, Chromy BA, Edwards C, Freed R, Liosatos M, Morgan TE, Rozovsky I, Trommer B, Viola KL, Wals P, Zhang C, Finch CE, Krafft GA, Klein WL. (1998). Diffusible, nonfibrillar ligands derived from Aβ1-42 are potent central nervous system neurotoxins. Proc Natl Acad Sci U S A, 95(11):6448-53.

Wang HW, Pasternak JF, Kuo H, Ristic H, Lambert MP, Chromy B, Viola KL, Klein WL, Stine WB, Krafft GA, Trommer BL. Soluble oligomers of beta amyloid (1-42) inhibit long-term potentiation but not long-term depression in rat dentate gyrus. Brain research. 2002;924(2):133-40.

Determination that brain-derived and synthetic AβOs are structurally homologous.
Gong Y, Chang L, Viola KL, Lacor PN, Lambert MP, Finch CE, Krafft GA, Klein WL. (2003). Alzheimer’s disease-affected brain: presence of oligomeric Aβ ligands (ADDLs) suggests a molecular basis for reversible memory loss. Proc Natl Acad Sci U S A, (18):10417-22.

Findings that AβOs induce major facets of AD pathology, including synapse degeneration, tau hyper-phosphorylation, selective nerve cell death, inflammatory glial activation, ER stress, and altered trafficking of receptors and membrane proteins.
Lacor PN, Buniel MC, Furlow PW, Clemente AS, Velasco PT, Wood M, Viola KL, Klein WL. (2007). Aβ oligomer-induced aberrations in synapse composition, shape, and density provide a molecular basis for loss of connectivity in Alzheimer’s disease. J Neurosci, 27(4):796-807.

De Felice FG, Wu D, Lambert MP, Fernandez SJ, Velasco PT, Lacor PN, Bigio EH, Jerecic J, Acton PJ, Shughrue PJ, Chen-Dodson E, Kinney GG, Klein WL. Alzheimer’s disease-type neuronal tau hyperphosphorylation induced by A beta oligomers. Neurobiology of aging. 2008;29(9):1334-47. doi: 10.1016/j.neurobiolaging.2007.02.029

Kim HJ, Chae SC, Lee DK, Chromy B, Lee SC, Park YC, Klein WL, Krafft GA, Hong ST. Selective neuronal degeneration induced by soluble oligomeric amyloid beta protein. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2003;17(1):118-20. doi: 10.1096/fj.01-0987fje

Welikovitch LA, Do Carmo S, Magloczky Z, Malcolm JC, Loke J, Klein WL, Freund T, Cuello AC. Early intraneuronal amyloid triggers neuron-derived inflammatory signaling in APP transgenic rats and human brain. Proceedings of the National Academy of Sciences of the United States of America. 2020;117(12):6844-54. doi: 10.1073/pnas.1914593117

Umeda T, Tomiyama T, Sakama N, Tanaka S, Lambert MP, Klein WL, Mori H. Intraneuronal amyloid beta oligomers cause cell death via endoplasmic reticulum stress, endosomal/lysosomal leakage, and mitochondrial dysfunction in vivo. Journal of neuroscience research. 2011;89(7):1031-42. doi: 10.1002/jnr.22640

Costa RO, Lacor PN, Ferreira IL, Resende R, Auberson YP, Klein WL, Oliveira CR, Rego AC, Pereira CM. Endoplasmic reticulum stress occurs downstream of GluN2B subunit of N-methyl-d-aspartate receptor in mature hippocampal cultures treated with amyloid-beta oligomers. Aging cell. 2012;11(5):823-33. doi: 10.1111/j.1474-9726.2012.00848.x

Decker H, Jurgensen S, Adrover MF, Brito-Moreira J, Bomfim TR, Klein WL, Epstein AL, De Felice FG, Jerusalinsky D, Ferreira ST. N-methyl-D-aspartate receptors are required for synaptic targeting of Alzheimer’s toxic amyloid-beta peptide oligomers. Journal of neurochemistry. 2010;115(6):1520-9. doi: 10.1111/j.1471-4159.2010.07058.x

Validation that the AβO hypothesis is disease-relevant, showing AD-dependent buildup of AβOs in human brain and CSF and in animal AD models.
Lambert MP, Barlow AK, Chromy BA, Edwards C, Freed R, Liosatos M, Morgan TE, Rozovsky I, Trommer B, Viola KL, Wals P, Zhang C, Finch CE, Krafft GA, Klein WL. (1998). Diffusible, nonfibrillar ligands derived from Aβ1-42 are potent central nervous system neurotoxins. Proc Natl Acad Sci U S A, 95(11):6448-53.

Klein WL. Probing for Aβ Oligomers in Brain and CSF. In: Nordberg A, editor. Nobel Forum on Early Alzheimer’s Imaging; Stockholm, Sweden (2015).
Viola KL, Klein WL. (2015) Amyloid β oligomers in Alzheimer’s disease pathogenesis, treatment, and diagnosis. Acta Neuropathol. 129(2):183-206. doi: 10.1007/s00401-015-1386-3.

Chang L, Bakhos L, Wang Z, Venton DL, Klein WL. Femtomole immunodetection of synthetic and endogenous amyloid-beta oligomers and its application to Alzheimer’s disease drug candidate screening. Journal of molecular neuroscience : MN. 2003;20(3):305-13. doi: 10.1385/JMN:20:3:305

Oddo S, Caccamo A, Tran L, Lambert MP, Glabe CG, Klein WL, LaFerla FM. Temporal profile of amyloid-beta (Abeta) oligomerization in an in vivo model of Alzheimer disease. A link between Abeta and tau pathology. The Journal of biological chemistry. 2006;281(3):1599-604. doi: 10.1074/jbc.M507892200

Discovery that AβOs act as specific ligands that bind to certain synapses.
Lacor PN, Buniel MC, Chang L, Fernandez SJ, Gong Y, Viola KL, Lambert MP, Velasco PT, Bigio EH, Finch CE, Krafft GA, Klein WL. (2004) Synaptic targeting by Alzheimer’s-related amyloid β oligomers. J Neurosci, 24(45):10191-200.

Introduction of the receptor hypothesis as a mechanism for AβO toxicity, with signaling dysfunction impacting Fyn, Arc, Ca++, ROS and ER stress.
Klein WL, Lacor PN, De Felice FG, Ferreira ST. Molecules that Disrupt Memory Circuits in Alzheimer’s Disease: The Attack on Synapses by Aβ Oligomers (ADDLs). In: Bontempi B, Silva AJ, Christen Y, editors. Memories: Molecules and Circuits. Berlin, Heidelberg: Springer Berlin Heidelberg; 2007. p. 155-79.

Cline EN, Bicca MA, Viola KL, Klein WL. (2018). The Amyloid-β Oligomer Hypothesis: Beginning of the Third Decade. J Alzheimers Dis. 64(s1):S567-S610. doi: 10.3233/JAD-179941.

Introduction of the first AβO-selective antibodies, shared with hundreds of other investigators.
Lambert MP, Viola KL, Chromy BA, Chang L, Morgan TE, Yu J, Venton DL, Krafft GA, Finch CE, Klein WL. Vaccination with soluble Abeta oligomers generates toxicity-neutralizing antibodies. Journal of neurochemistry. 2001;79(3):595-605.

Proof that AβO antibodies can be used for MRI and PET imaging in animal AD models.
Viola KL, Sbarboro J, Sureka R, De M, Bicca MA, Wang J, Vasavada S, Satpathy S, Wu S, Joshi H, Velasco PT, MacRenaris K, Waters EA, Lu C, Phan J, Lacor P, Prasad P, Dravid VP, Klein WL. (2015). Towards non-invasive diagnostic imaging of early-stage Alzheimer’s disease. Nat Nanotechnol. 10(1):91-8. doi: 10.1038/nnano.2014.254.

Demonstration that AβO antibodies can rescue memory function in animal AD models.
Viola KL, Bicca MA, Bebenek AM, Kranz DL, Nandwana V, Waters EA, Haney CR, Lee M, Gupta A, Brahmbhatt Z, Huang W, Chang TT, Peck A, Valdez C, Dravid VP, Klein WL. The Therapeutic and Diagnostic Potential of Amyloid β Oligomers Selective Antibodies to Treat Alzheimer’s Disease. Front Neurosci. 2022 Jan 3;15:768646. doi: 10.3389/fnins.2021.768646.

Discovery that transiently expressed AβOs play a role in CNS development.
Bartley SC, Proctor MT, Xia H, Ho E, Kang DS, Schuster K, Bicca MA, Seckler HS, Viola KL, Patrie SM, Kelleher NL, De Mello FG, Klein WL. An Essential Role for Alzheimer’s-Linked Amyloid Beta Oligomers in Neurodevelopment: Transient Expression of Multiple Proteoforms during Retina Histogenesis. International journal of molecular sciences. 2022;23(4). Epub 2022/02/27. doi: 10.3390/ijms23042208

Successful completion of Phase 1 of the “Intercept-AD” clinical trial by Acumen (an Alzheimer’s biotech I co-founded), which tests an AβO monoclonal antibody, sabirnetug (ACU193), that was developed based on original research from my team at Northwestern.
Siemers E, Hitchcock J, Sundell K, Dean R, Jerecic J, Cline E, Iverson K, Moore J, Edgar C, Manber R. ACU193, a Monoclonal Antibody that Selectively Binds Soluble Aβ Oligomers: Development Rationale, Phase 1 Trial Design, and Clinical Development Plan. The journal of prevention of Alzheimer’s disease. 2023;10(1):19-24.

Westwicke I. Acumen Pharmaceuticals to Present Sabirnetug (ACU193) Fluid Biomarker and Target Engagement Analyses from Phase 1 INTERCEPT-AD Study in Early Alzheimer’s at the AD/PD™ 2024 Annual Meeting. In: Acumen Pharmaceuticals I, editor. https://investors.acumenpharm.com/news-releases/news-release-details/acumen-pharmaceuticals-present-sabirnetug-acu193-fluid-biomarker: Globe Newswire; 2024.