Natural oligomers of the amyloid-β protein specifically disrupt cognitive function
10.1038/nn1372
Crossref journal-article
Springer Science and Business Media LLC
Nature Neuroscience (297)
Bibliography

Cleary, J. P., Walsh, D. M., Hofmeister, J. J., Shankar, G. M., Kuskowski, M. A., Selkoe, D. J., & Ashe, K. H. (2004). Natural oligomers of the amyloid-β protein specifically disrupt cognitive function. Nature Neuroscience, 8(1), 79–84.

Authors 7
  1. James P Cleary (first)
  2. Dominic M Walsh (additional)
  3. Jacki J Hofmeister (additional)
  4. Ganesh M Shankar (additional)
  5. Michael A Kuskowski (additional)
  6. Dennis J Selkoe (additional)
  7. Karen H Ashe (additional)
References 46 Referenced 1,405
  1. Hardy, J. & Allsop, D. Amyloid deposition as the central event in the aetiology of Alzheimer's disease. Trends Pharmacol. Sci. 12, 383–388 (1991). (10.1016/0165-6147(91)90609-V) / Trends Pharmacol. Sci. by J Hardy (1991)
  2. Selkoe, D. The molecular pathology of Alzheimer's disease. Neuron 6, 487–498 (1991). (10.1016/0896-6273(91)90052-2) / Neuron by D Selkoe (1991)
  3. Price, J.L., Davis, P.B., Morris, J.C. & White, D.L. The distribution of tangles, plaques and related immunohistochemical markers in healthy aging and Alzheimer's disease. Neurobiol. Aging 12, 295–312 (1991). (10.1016/0197-4580(91)90006-6) / Neurobiol. Aging by JL Price (1991)
  4. Lorenzo, A. & Yankner, B.A. β-amyloid neurotoxicity requires fibril formation and is inhibited by congo red. Proc. Natl. Acad. Sci. USA 91, 12243–12247 (1994). (10.1073/pnas.91.25.12243) / Proc. Natl. Acad. Sci. USA by A Lorenzo (1994)
  5. Cummings, B.J. & Cotman, C.W. Image analysis of β-amyloid load in Alzheimer's disease and relation to dementia severity. Lancet 346, 1524–1528 (1995). (10.1016/S0140-6736(95)92053-6) / Lancet by BJ Cummings (1995)
  6. McLean, C.A. et al. Soluble pool of Aβ amyloid as a determinant of severity of neurodegeneration in Alzheimer's disease. Ann. Neurol. 46, 860–866 (1999). (10.1002/1531-8249(199912)46:6<860::AID-ANA8>3.0.CO;2-M) / Ann. Neurol. by CA McLean (1999)
  7. Naslund, J. et al. Correlation between elevated levels of amyloid β-peptide in the brain and cognitive decline. J. Am. Med. Assoc. 283, 1571–1577 (2000). (10.1001/jama.283.12.1571) / J. Am. Med. Assoc. by J Naslund (2000)
  8. Pike, C.J., Walencewicz, A.J., Glabe, C.G. & Cotman, C.W. Aggregation-related toxicity of synthetic β-amyloid protein in hippocampal cultures. Eur. J. Pharmacol. 207, 367–368 (1991). (10.1016/0922-4106(91)90014-9) / Eur. J. Pharmacol. by CJ Pike (1991)
  9. Irizarry, M.C., McNamara, M., Fedorchak, K., Hsiao, K. & Hyman, B.T. APPSw transgenic mice develop age-related A β deposits and neuropil abnormalities, but no neuronal loss in CA1. J. Neuropathol. Exp. Neurol. 56, 965–973 (1997). (10.1097/00005072-199709000-00002) / J. Neuropathol. Exp. Neurol. by MC Irizarry (1997)
  10. Irizarry, M.C. et al. Aβ deposition is associated with neuropil changes, but not with overt neuronal loss in the human amyloid precursor protein V717F (PDAPP) transgenic mouse. J. Neurosci. 17, 7053–7059 (1997). (10.1523/JNEUROSCI.17-18-07053.1997) / J. Neurosci. by MC Irizarry (1997)
  11. Moechars, D., Lorent, K., De Strooper, B., Dewachter, I. & Van Leuven, F. Expression in brain of amyloid precursor protein mutated in the α-secretase site causes disturbed behavior, neuronal degeneration and premature death in transgenic mice. EMBO J. 15, 1265–1274 (1996). (10.1002/j.1460-2075.1996.tb00468.x) / EMBO J. by D Moechars (1996)
  12. Westerman, M.A. et al. The relationship between Aβ and memory in the Tg2576 mouse model of Alzheimer's disease. J. Neurosci. 22, 1858–1867 (2002). (10.1523/JNEUROSCI.22-05-01858.2002) / J. Neurosci. by MA Westerman (2002)
  13. Terry, R.D. et al. Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment. Ann. Neurol. 30, 572–580 (1991). (10.1002/ana.410300410) / Ann. Neurol. by RD Terry (1991)
  14. Dickson, D.W. et al. Correlations of synaptic and pathological markers with cognition of the elderly. Neurobiol. Aging 16, 285–298 (1995). (10.1016/0197-4580(95)00013-5) / Neurobiol. Aging by DW Dickson (1995)
  15. Katzman, R. et al. Clinical, pathological, and neurochemical changes in dementia: a subgroup with preserved mental status and numerous neocortical plaques. Ann. Neurol. 23, 138–144 (1988). (10.1002/ana.410230206) / Ann. Neurol. by R Katzman (1988)
  16. Delaere, P. et al. Large amounts of neocortical β A4 deposits without neuritic plaques nor tangles in a psychometrically assessed, non-demented person. Neurosci. Lett. 116, 87–93 (1990). (10.1016/0304-3940(90)90391-L) / Neurosci. Lett. by P Delaere (1990)
  17. Stern, E.A. et al. Cortical synaptic integration in vivo is disrupted by amyloid-β plaques. J. Neurosci. 24, 4535–4540 (2004). (10.1523/JNEUROSCI.0462-04.2004) / J. Neurosci. by EA Stern (2004)
  18. Walsh, D.M. et al. Naturally secreted oligomers of amyloid β protein potently inhibit hippocampal long-term potentiation in vivo. Nature 416, 535–539 (2002). (10.1038/416535a) / Nature by DM Walsh (2002)
  19. Wang, H.W. et al. Soluble oligomers of β amyloid (1-42) inhibit long-term potentiation but not long-term depression in rat dentate gyrus. Brain Res. 924, 133–140 (2002). (10.1016/S0006-8993(01)03058-X) / Brain Res. by HW Wang (2002)
  20. Wang, Q., Walsh, D.M., Rowan, M., Selkoe, D. & Anwyl, R. β-amyloid induced inhibition of LTP induction involves activation of mGluR5 and the kinases JNK, cdk5 and p38 MAPK. J. Neurosci. 24, 3370–3378 (2004). (10.1523/JNEUROSCI.1633-03.2004) / J. Neurosci. by Q Wang (2004)
  21. Dudai, Y. Memory from A to Z: Keywords, Concepts and Beyond (Oxford Univ. Press, 2002). (10.1093/oso/9780198502678.001.0001) / Memory from A to Z: Keywords, Concepts and Beyond by Y Dudai (2002)
  22. Hsia, A.Y. et al. Plaque-independent disruption of neural circuits in Alzheimer's disease mouse models. Proc. Natl. Acad. Sci. USA 96, 3228–3233 (1999). (10.1073/pnas.96.6.3228) / Proc. Natl. Acad. Sci. USA by AY Hsia (1999)
  23. Kotilinek, L.A. et al. Reversible memory loss in a mouse transgenic model of Alzheimer's disease. J. Neurosci. 22, 6331–6335 (2002). (10.1523/JNEUROSCI.22-15-06331.2002) / J. Neurosci. by LA Kotilinek (2002)
  24. Dodart, J.C. et al. Immunization reverses memory deficits without reducing brain Aβ burden in Alzheimer's disease model. Nat. Neurosci. 5, 452–457 (2002). (10.1038/nn842) / Nat. Neurosci. by JC Dodart (2002)
  25. Walsh, D.M., Tseng, B.P., Rydel, R.E., Podlisny, M.B. & Selkoe, D.J. The oligomerization of amyloid β-protein begins intracellularly in cells derived from human brain. Biochemistry 39, 10831–10839 (2000). (10.1021/bi001048s) / Biochemistry by DM Walsh (2000)
  26. Weldon, D.T., O'Hare, E., Kuskowski, M.A., Cleary, J. & Mach, J.R. Jr. Alternating lever cyclic-ratio schedule analysis of the effects of atropine sulfate. Pharmacol. Biochem. Behav. 54, 753–757 (1996). (10.1016/0091-3057(96)00014-7) / Pharmacol. Biochem. Behav. by DT Weldon (1996)
  27. O'Hare, E. et al. Utilization of a novel model of food reinforced behavior involving neuropeptide Y, insulin, 2-deoxy-D-glucose and naloxone. Behav. Pharmacol. 7, 742–753 (1996). / Behav. Pharmacol. by E O'Hare (1996)
  28. Richardson, R.L. et al. Behavioural and histopathological analyses of ibuprofen treatment on the effect of aggregated Aβ(1-42) injections in the rat. Brain Res. 954, 1–10 (2002). (10.1016/S0006-8993(02)03006-8) / Brain Res. by RL Richardson (2002)
  29. Pedersen, E.S., Krishnan, R., Harding, J.W. & Wright, J.W. A role for the angiotensin AT4 receptor subtype in overcoming scopolamine induced spatial memory deficits. Regul. Pept. 102, 147–156 (2001). (10.1016/S0167-0115(01)00312-3) / Regul. Pept. by ES Pedersen (2001)
  30. Mishima, K. et al. The scopolamine-induced impairment of spatial cognition parallels the acetylcholine release in the ventral hippocampus in rats. Jpn. J. Pharmacol. 84, 163–173 (2000). (10.1254/jjp.84.163) / Jpn. J. Pharmacol. by K Mishima (2000)
  31. Klein, W.L., Krafft, G.A. & Finch, C.E. Targeting small Aβ oligomers: the solution to an Alzheimer's disease conundrum? Trends Neurosci. 24, 219–224 (2001). (10.1016/S0166-2236(00)01749-5) / Trends Neurosci. by WL Klein (2001)
  32. Selkoe, D.J. Alzheimer's disease is a synaptic failure. Science 298, 789–791 (2002). (10.1126/science.1074069) / Science by DJ Selkoe (2002)
  33. Walsh, D.M., Hartley, D.M. & Selkoe, D.J. The many faces of Aβ: structures and function. Curr. Med. Chem. Immunol. Endocr. Metab. Agents 3, 277–291 (2003). (10.2174/1568013033483311) / Curr. Med. Chem. Immunol. Endocr. Metab. Agents by DM Walsh (2003)
  34. O'Hare, E. et al. Delayed behavioral effects following intrahippocampal injection of aggregated A β (1-42). Brain Res. 815, 1–10 (1999). (10.1016/S0006-8993(98)01002-6) / Brain Res. by E O'Hare (1999)
  35. Cleary, J., Hittner, J.M., Semotuk, M., Mantyh, P. & O'Hare, E. β-amyloid(1-40) effects on behavior and memory. Brain Res. 682, 69–74 (1995). (10.1016/0006-8993(95)00323-I) / Brain Res. by J Cleary (1995)
  36. Frautschy, S.A. et al. Phenolic anti-inflammatory antioxidant reversal of Aβ-induced cognitive deficits and neuropathology. Neurobiol. Aging 22, 993–1005 (2001). (10.1016/S0197-4580(01)00300-1) / Neurobiol. Aging by SA Frautschy (2001)
  37. Sweeney, W.A., Luedtke, J., McDonald, M.P. & Overmier, J.B. Intrahippocampal injections of exogenous β-amyloid induce postdelay errors in an eight-arm radial maze. Neurobiol. Learn. Mem. 68, 97–101 (1997). (10.1006/nlme.1997.3770) / Neurobiol. Learn. Mem. by WA Sweeney (1997)
  38. McDonald, M.P., Dahl, E.E., Overmier, J.B., Mantyh, P. & Cleary, J. Effects of an exogenous β-amyloid peptide on retention for spatial learning. Behav. Neural Biol. 62, 60–67 (1994). (10.1016/S0163-1047(05)80059-7) / Behav. Neural Biol. by MP McDonald (1994)
  39. Geula, C. et al. Aging renders the brain vulnerable to amyloid β-protein neurotoxicity. Nat. Med. 4, 827–831 (1998). (10.1038/nm0798-827) / Nat. Med. by C Geula (1998)
  40. Bookheimer, S.Y. et al. Patterns of brain activation in people at risk for Alzheimer's disease. N. Engl. J. Med. 343, 450–456 (2000). (10.1056/NEJM200008173430701) / N. Engl. J. Med. by SY Bookheimer (2000)
  41. Small, G.W. et al. Cerebral metabolic and cognitive decline in persons at genetic risk for Alzheimer's disease. Proc. Natl. Acad. Sci. USA 97, 6037–6042 (2000). (10.1073/pnas.090106797) / Proc. Natl. Acad. Sci. USA by GW Small (2000)
  42. Chen, G. et al. A learning deficit related to age and β-amyloid plaques in a mouse model of Alzheimer's disease. Nature 408, 975–979 (2000). (10.1038/35050103) / Nature by G Chen (2000)
  43. Koistinaho, M. et al. Specific spatial learning deficits become severe with age in β-amyloid precursor protein transgenic mice that harbor diffuse β-amyloid deposits but do not form plaques. Proc. Natl. Acad. Sci. USA 98, 14675–14680 (2001). (10.1073/pnas.261562998) / Proc. Natl. Acad. Sci. USA by M Koistinaho (2001)
  44. Palop, J.J. et al. Neuronal depletion of calcium-dependent proteins in the dentate gyrus is tightly linked to Alzheimer's disease-related cognitive deficits. Proc. Natl. Acad. Sci. USA 100, 9572–9577 (2003). (10.1073/pnas.1133381100) / Proc. Natl. Acad. Sci. USA by JJ Palop (2003)
  45. Hsiao, K. et al. Correlative memory deficits, Aβ elevation, and amyloid plaques in transgenic mice. Science 274, 99–102 (1996). (10.1126/science.274.5284.99) / Science by K Hsiao (1996)
  46. Johnson-Wood, K. et al. Amyloid precursor protein processing and A β42 deposition in a transgenic mouse model of Alzheimer disease. Proc. Natl. Acad. Sci. USA 94, 1550–1555 (1997). (10.1073/pnas.94.4.1550) / Proc. Natl. Acad. Sci. USA by K Johnson-Wood (1997)
Dates
Type When
Created 20 years, 8 months ago (Dec. 19, 2004, 1:16 p.m.)
Deposited 1 year, 7 months ago (Jan. 16, 2024, 9:38 p.m.)
Indexed 2 days, 19 hours ago (Sept. 3, 2025, 6:08 a.m.)
Issued 20 years, 8 months ago (Dec. 19, 2004)
Published 20 years, 8 months ago (Dec. 19, 2004)
Published Online 20 years, 8 months ago (Dec. 19, 2004)
Published Print 20 years, 8 months ago (Jan. 1, 2005)
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@article{Cleary_2004, title={Natural oligomers of the amyloid-β protein specifically disrupt cognitive function}, volume={8}, ISSN={1546-1726}, url={http://dx.doi.org/10.1038/nn1372}, DOI={10.1038/nn1372}, number={1}, journal={Nature Neuroscience}, publisher={Springer Science and Business Media LLC}, author={Cleary, James P and Walsh, Dominic M and Hofmeister, Jacki J and Shankar, Ganesh M and Kuskowski, Michael A and Selkoe, Dennis J and Ashe, Karen H}, year={2004}, month=dec, pages={79–84} }