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What are ADDLs?
Why are they relevant?
How can they be treated?
Intellectual Property
Acumen Publications
Other Publications
Acumen Presentations |
Key Publications Pertaining to ADDLs and Alzheimer’s disease
 Acumen’s founders first discovered ADDLs in 1995, reported their potent ability to block memory related long term potentiation (LTP) in 1998, and proposed a new hypothesis for Alzheimer’s disease based on ADDL disruption of synaptic function rather than non-specific cellular damage cause by fibrillar ß deposits. This hypothesis led to the development of immune-based strategies to block ADDL activity and reverse Alzheimer’s disease symptoms (Klein et al, 2001). In late 2003, the presence of ADDLs in an Alzheimer’s disease brain was first reported, with levels 70-fold higher than in age-matched controls (Gong et al, 2003). More recently, direct ADDL binding to post-synaptic dendritic spines, accompanied by rapid and persistent up-regulation of the memory-related gene arc was described (Lacor et al, 2004). The rapid compromise of memory induced by direct injection of Aβ oligomers from Aβ-overproducing cells has been recently reported (Cleary et al, 2005), and these deficits have now been shown to be caused specifically by the 12-mer ADDL species (Lesne et al, 2006). Collectively, these studies provide compelling evidence that ADDLs are responsible for memory loss in Alzheimer’s disease and they provide strong rationale to pursue ADDL-directed therapeutics.
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Acumen Publications
- Diffusible, nonfibrillar ligands derived from Aß 1–42 are potent central nervous system neurotoxins
M. P. Lambert, A. K. Barlow, B. A. Chromy, E. Edwards, R. Freed, M Liosatos, T. E. Morgan, I. Rozovsky, B. Trommer, K. L. Viola, P. Wals, C. Zhang, C. E. Finch, G. A. Krafft, and W. L. Klein
Proceedings of the National Academy of Science USA (1998) Vol. 95, 6448–6453; [Abstract] [Full Paper]
- Vaccination with soluble Aß oligomers generates toxicity-neutralizing antibodies
Mary P. Lambert, Kirsten L. Viola, Brett A. Chromy, Lei Chang, Todd E. Morgan, Jiaxin Yu, Duane L. Venton, Grant A. Krafft, Caleb E. Finch and William L. Klein
Journal of Neurochemistry (2001) Vol. 79, 595- 605;
[Abstract] [Full Paper]
- Soluble oligomers of ß amyloid (1-42) inhibit long-term potentiation but not long-term depression in rat dentate gyrus
Hai-Wei Wang, Joseph F. Pasternak, Helen Kuo, Helen Ristic, Mary P. Lambert, Brett Chromy, Kirsten L. Viola, William L. Klein, W. Blaine Stine, Grant A. Krafft, Barbara L. Trommer
Brain Research (2002) Vol. 924, 133–140;
[Abstract] [Full Paper]
- Oligomeric and Fibrillar Species of Amyloid-ß Peptides Differentially Affect Neuronal Viability
Karie N. Dahlgren, Arlene M. Manelli, W. Blaine Stine, Jr, Lorinda K. Baker, Grant A. Krafft, and Mary Jo LaDu
The Journal of Biological Chemistry (2002) Vol. 277, No. 35, 32046–32053 [Abstract] [Full Paper]
- Emerging Themes in Alzheimer’s Disease Research: Paradigm Shift in Drug Discovery
Todd E. Morgan and Grant A. Krafft
Annual Reports in Medicinal Chemistry (2002) Vol. 37, Chapter 4 [Abstract] [Full Paper]
- Self-Assembly of Aß1-42 into Globular Neurotoxins
Brett A. Chromy, Richard J. Nowak, Mary P. Lambert, Kirsten L. Viola, Lei Chang, Pauline T. Velasco, Bryan W. Jones, Sara J. Fernandez, Pascale N. Lacor, Peleg Horowitz, Caleb E. Finch,| Grant A. Krafft, and William L. Klein
Biochemistry (2003) Vol. 42, 12749-12760
[Abstract] [Full Paper]
- Alzheimer’s disease-affected brain: Presence of oligomeric Aß ligands (ADDLs) suggests a molecular basis for reversible memory loss
Yuesong Gong, Lei Chang, Kirsten L. Viola, Pascale N. Lacor, Mary P. Lambert, Caleb E. Finch, Grant A. Krafft, and William L. Klein
Proceedings of the National Academy of Sciences (2003) Vol. 100, No. 18, 10417–10422 [Abstract] [Full Paper]
- Selective neuronal degeneration induced by soluble oligomeric amyloid beta protein
Hyeon-Jin Kim, Soo-Cheon Chae, Dae-Kwon Lee, Brett Chromy, Sam Sheol Lee, Yeong-Chul Park, William L. Klein, Grant A. Krafft, and Seong-Tshool Hong
The FASEB Journal (2003) Vol. 17,118-120
[Abstract] [Full Paper]
- In Vitro Characterization of Conditions for Amyloid-β Peptide Oligomerization and Fibrillogenesis
W. Blaine Stine, Jr., Karie N. Dahlgren, Grant A. Krafft, and Mary Jo LaDu
The Journal of Biological Chemistry (2003) Vol. 278, No. 13, 11612-11622 [Abstract] [Full Paper]
- Synaptic Targeting by Alzheimer’s-Related Amyloid β Oligomers
Pascale N. Lacor, Maria C. Buniel, Lei Chang, Sara J. Fernandez, Yuesong Gong, Kirsten L. Viola, Mary P. Lambert, Pauline T. Velasco, Eileen H. Bigio, Caleb E. Finch, Grant A. Krafft, and William L. Klein
The Journal of Neuroscience (2004) Vol. 24, No. 45, 10191–10200 [Abstract] [Full Paper]
- Targeting small Aβ oligomers: the solution to an Alzheimer’s disease conundrum?
William L. Klein, Grant A. Krafft and Caleb E. Finch
Trends in Neurosciences Vol.24 No.4 April 2001
[Abstract] [Full Review]
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