Immunological and Anti-chaperone Therapeutic Approaches for Alzheimer Disease

Overview

Journal Brain Pathol

Date 2005 Mar 23

PMID 15779239

Citations 28

Authors

Thomas Wisniewski

Blas Frangione

Affiliations

Soon will be listed here.

Abstract

Alzheimer disease (AD) is the most common cause of dementia. Currently available therapies only provide symptomatic relief. A number of therapeutic approaches are under development that aim to increase the clearance of brain Abeta peptides. These include immune mediated clearance of Abeta and the inhibition of the interaction between Abeta and its pathological chaperones. Both active and passive immunization has been shown to have robust effects in transgenic mouse models of AD on amyloid reduction and behavioral improvements. However, a human trial of active immunization has been associated with significant toxicity in a minority of patients. New generation vaccines are being developed which likely will reduce the potential for cell-mediated toxicity. In addition, the recent development of anti-chaperone therapy opens a new therapeutic avenue which is unlikely to be associated with toxicity.

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References

Barrow C, Yasuda A, Kenny P, Zagorski M . Solution conformations and aggregational properties of synthetic amyloid beta-peptides of Alzheimer's disease. Analysis of circular dichroism spectra. J Mol Biol. 1992; 225(4):1075-93. DOI: 10.1016/0022-2836(92)90106-t. View

Boyett K, DiCarlo G, Jantzen P, Jackson J, OLeary C, Wilcock D . Increased fibrillar beta-amyloid in response to human clq injections into hippocampus and cortex of APP+PS1 transgenic mice. Neurochem Res. 2003; 28(1):83-93. DOI: 10.1023/a:1021600212829. View

Pappolla M, Bozner P, Soto C, Shao H, Robakis N, Zagorski M . Inhibition of Alzheimer beta-fibrillogenesis by melatonin. J Biol Chem. 1998; 273(13):7185-8. DOI: 10.1074/jbc.273.13.7185. View

Ingelsson M, Fukumoto H, Newell K, Growdon J, Hedley-Whyte E, Frosch M . Early Abeta accumulation and progressive synaptic loss, gliosis, and tangle formation in AD brain. Neurology. 2004; 62(6):925-31. DOI: 10.1212/01.wnl.0000115115.98960.37. View

Sanan D, Weisgraber K, Russell S, Mahley R, Huang D, Saunders A . Apolipoprotein E associates with beta amyloid peptide of Alzheimer's disease to form novel monofibrils. Isoform apoE4 associates more efficiently than apoE3. J Clin Invest. 1994; 94(2):860-9. PMC: 296168. DOI: 10.1172/JCI117407. View

Robinson S, Bishop G, Lee H, Munch G . Lessons from the AN 1792 Alzheimer vaccine: lest we forget. Neurobiol Aging. 2004; 25(5):609-15. DOI: 10.1016/j.neurobiolaging.2003.12.020. View

Tomiyama T, Shoji A, Kataoka K, Suwa Y, Asano S, Kaneko H . Inhibition of amyloid beta protein aggregation and neurotoxicity by rifampicin. Its possible function as a hydroxyl radical scavenger. J Biol Chem. 1996; 271(12):6839-44. DOI: 10.1074/jbc.271.12.6839. View

Janus C, Pearson J, McLaurin J, Mathews P, Jiang Y, Schmidt S . A beta peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer's disease. Nature. 2001; 408(6815):979-82. DOI: 10.1038/35050110. View

Zhang J, Wu X, Qin C, Qi J, Ma S, Zhang H . A novel recombinant adeno-associated virus vaccine reduces behavioral impairment and beta-amyloid plaques in a mouse model of Alzheimer's disease. Neurobiol Dis. 2003; 14(3):365-79. DOI: 10.1016/j.nbd.2003.07.005. View

10.

Wisniewski T, Golabek A, Matsubara E, Ghiso J, Frangione B . Apolipoprotein E: binding to soluble Alzheimer's beta-amyloid. Biochem Biophys Res Commun. 1993; 192(2):359-65. DOI: 10.1006/bbrc.1993.1423. View

11.

Crawford F, Vanderploeg R, Freeman M, Singh S, WAISMAN M, Michaels L . APOE genotype influences acquisition and recall following traumatic brain injury. Neurology. 2002; 58(7):1115-8. DOI: 10.1212/wnl.58.7.1115. View

12.

Weisgraber K, Mahley R . Human apolipoprotein E: the Alzheimer's disease connection. FASEB J. 1996; 10(13):1485-94. DOI: 10.1096/fasebj.10.13.8940294. View

13.

Monsonego A, Weiner H . Immunotherapeutic approaches to Alzheimer's disease. Science. 2003; 302(5646):834-8. DOI: 10.1126/science.1088469. View

14.

Lemere C, Maron R, Selkoe D, Weiner H . Nasal vaccination with beta-amyloid peptide for the treatment of Alzheimer's disease. DNA Cell Biol. 2002; 20(11):705-11. DOI: 10.1089/10445490152717569. View

15.

Miller D, Currie J, Mehta P, Potempska A, Hwang Y, Wegiel J . Humoral immune response to fibrillar beta-amyloid peptide. Biochemistry. 2003; 42(40):11682-92. DOI: 10.1021/bi030100s. View

16.

Schenk D, Barbour R, Dunn W, Gordon G, Grajeda H, Guido T . Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature. 1999; 400(6740):173-7. DOI: 10.1038/22124. View

17.

Sigurdsson E, Wisniewski T, Frangione B . A safer vaccine for Alzheimer's disease?. Neurobiol Aging. 2002; 23(6):1001-8. DOI: 10.1016/s0197-4580(02)00124-0. View

18.

Bacskai B, Kajdasz S, Christie R, Carter C, Games D, Seubert P . Imaging of amyloid-beta deposits in brains of living mice permits direct observation of clearance of plaques with immunotherapy. Nat Med. 2001; 7(3):369-72. DOI: 10.1038/85525. View

19.

Reisberg B, Doody R, Stoffler A, Schmitt F, Ferris S, Mobius H . Memantine in moderate-to-severe Alzheimer's disease. N Engl J Med. 2003; 348(14):1333-41. DOI: 10.1056/NEJMoa013128. View

20.

Farrer L, Cupples L, Haines J, Hyman B, Kukull W, Mayeux R . Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. JAMA. 1997; 278(16):1349-56. View