Amyloid β and Alzheimer disease therapeutics: the devil may be in the details

Alzheimer disease (AD) is characterized by the progressive accumulation of amyloid β protein (Aβ) in areas of the brain serving cognitive functions such as memory and language. The first of two separate reports (see the related articles beginning on pages 415 and 440) reveals that intrinsic T cell reactivity to the self-antigen Aβ exists in many humans and increases with age. This finding has implications for the design of Aβ vaccines. The second report demonstrates that a number of FDA- approved nonsteroidal anti-inflammatory drugs are capable of lowering Aβ levels in mice. The work suggests that further testing of the therapeutic utility of these types of compounds for the potential treatment of AD is warranted.

[1]  R. Sperling,et al.  Increased T cell reactivity to amyloid beta protein in older humans and patients with Alzheimer disease. , 2003, The Journal of clinical investigation.

[2]  Pritam Das,et al.  NSAIDs and enantiomers of flurbiprofen target γ-secretase and lower Aβ42 in vivo , 2003 .

[3]  Ping Liu,et al.  In vivo antiviral efficacy of prenylation inhibitors against hepatitis delta virus. , 2003, The Journal of clinical investigation.

[4]  C. Holmes,et al.  Neuropathology of human Alzheimer disease after immunization with amyloid-β peptide: a case report , 2003, Nature Medicine.

[5]  R. Nitsch,et al.  Generation of antibodies specific for β-amyloid by vaccination of patients with Alzheimer disease , 2002, Nature Medicine.

[6]  B. Hyman,et al.  Reversible Memory Loss in a Mouse Transgenic Model of Alzheimer's Disease , 2002, The Journal of Neuroscience.

[7]  Xin Wu,et al.  Immunization reverses memory deficits without reducing brain Aβ burden in Alzheimer's disease model , 2002, Nature Neuroscience.

[8]  T. Town,et al.  Characterization of murine immunoglobulin G antibodies against human amyloid-β1–42 , 2001, Neuroscience Letters.

[9]  David J. Cummins,et al.  Peripheral anti-Aβ antibody alters CNS and plasma Aβ clearance and decreases brain Aβ burden in a mouse model of Alzheimer's disease , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[10]  G. Gaeta,et al.  Type B and D viral hepatitis: epidemiological changes in Southern Europe. , 2001, Forum.

[11]  Ralph A. Nixon,et al.  Aβ peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer's disease , 2000, Nature.

[12]  J. Hardy,et al.  Aβ peptide vaccination prevents memory loss in an animal model of Alzheimer's disease , 2000, Nature.

[13]  R. Motter,et al.  Peripherally administered antibodies against amyloid β-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease , 2000, Nature Medicine.

[14]  R. Motter,et al.  Immunization with amyloid-β attenuates Alzheimer-disease-like pathology in the PDAPP mouse , 1999, Nature.

[15]  J. Taylor,et al.  Ribonucleoprotein complexes of hepatitis delta virus , 1993, Journal of virology.

[16]  J. Casey,et al.  Structural requirements for RNA editing in hepatitis delta virus: evidence for a uridine-to-cytidine editing mechanism. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[17]  J. Glenn,et al.  Identification of a prenylation site in delta virus large antigen. , 1992, Science.

[18]  R. Purcell,et al.  The Size of the Hepatitis Delta Agent , 1989, Journal of medical virology.

[19]  J. Taylor,et al.  Antigenomic RNA of human hepatitis delta virus can undergo self-cleavage , 1988, Journal of virology.

[20]  M. Houghton,et al.  Structure, sequence and expression of the hepatitis delta (δ) viral genome , 1987, Nature.

[21]  R. Purcell,et al.  Transmission of the hepatitis B virus-associated delta antigen to chimpanzees. , 1980, The Journal of infectious diseases.

[22]  D. Holtzman,et al.  Peripheral anti-A beta antibody alters CNS and plasma A beta clearance and decreases brain A beta burden in a mouse model of Alzheimer's disease. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[23]  J. Hardy,et al.  A beta peptide vaccination prevents memory loss in an animal model of Alzheimer's disease. , 2000, Nature.

[24]  P. S. St George-Hyslop,et al.  A beta peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer's disease. , 2000, Nature.

[25]  W. Schafer,et al.  Protein prenylation: genes, enzymes, targets, and functions. , 1992, Annual review of genetics.

[26]  S. Hadziyannis.  Use of alpha-interferon in the treatment of chronic delta hepatitis. , 1991, Journal of hepatology.