journal article Nov 12, 2013

Alzheimer disease therapy—moving from amyloid-β to tau

View at Publisher Save 10.1038/nrneurol.2013.223
Topics

No keywords indexed for this article. Browse by subject →

References
88
[1]
Alzheimer's Disease: The Amyloid Cascade Hypothesis

John A. Hardy, Gerald A. Higgins

Science 1992 10.1126/science.1566067
[2]
Ferreira, S. T. & Klein, W. L. The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's disease. Neurobiol. Learn. Mem. 96, 529–543 (2011). 10.1016/j.nlm.2011.08.003
[3]
Giacobini, E. & Becker, R. E. One hundred years after discovery of Alzheimer's disease. A turning point for therapy? J. Alzheimers Dis. 12, 37–52 (2007). 10.3233/jad-2007-12105
[4]
Becker, R. E. & Greig, N. H. Why so few drugs for Alzheimer's disease? Are methods failing drugs? Curr. Alzheimer Res. 7, 27–35 (2010). 10.2174/156720510793499075
[5]
Becker, R. E., Greig, H. H. & Giacobini, E. Why do so many drugs for Alzheimer's disease fail in development? Time for new methods and new practices? J. Alzheimers Dis. 15, 303–325 (2008). 10.3233/jad-2008-15213
[6]
Becker, R. E. & Greig, H. H. Increasing the success rate for Alzheimer's disease drug discovery and development. Expert Opin. Drug Discov. 4, 367–370 (2012). 10.1517/17460441.2012.672409
[7]
Hardy, J. Testing times for the “amyloid cascade hypothesis”. Neurobiol. Aging 6, 1073–1074 (2002). 10.1016/s0197-4580(02)00042-8
[8]
Hardy, J. Alzheimer disease: the amyloid cascade hypothesis: an update and reappraisal. J. Alzheimers Dis. 9, 151–153 (2006). 10.3233/jad-2006-9s317
[9]
Xia, W., Wong, S. T., Hanlon, E. & Morin, P. γ-Secretase modulator in Alzheimer's disease: shifting the end. J. Alzheimers Dis. 31, 685–696 (2012). 10.3233/jad-2012-120751
[10]
Green, R. C. et al. Effect of tarenflurbil on cognitive decline and activities of daily living in patients with mild Alzheimer disease: a randomized controlled trial. JAMA 302, 2557–2564 (2009). 10.1001/jama.2009.1866
[11]
Henley, D. B., May, P. C., Dean, R. A. & Siemers, E. R. Development of semagacestat (LY450139), a functional gamma-secretase inhibitor, for the treatment of Alzheimer's disease. Exp. Opin. Pharmacother. 10, 1657–1674 (2009). 10.1517/14656560903044982
[12]
Eli Lilly and Company. Lilly halts development of semagacestat for Alzheimer's disease based on preliminary results of phase III clinical trials. Eli Lilly and Company[online], (2010).
[13]
Coric, V. et al. Safety and tolerability of the γ-secretase inhibitor avagacestat in a phase 2 study of mild to moderate Alzheimer disease. Arch. Neurol. 69, 1430–1440 (2012). 10.1001/archneurol.2012.2194
[14]
Atwal, J. K. et al. A therapeutic antibody targeting BACE1 inhibits amyloid-β production in vivo. Sci. Transl. Med. 3, 84ra43 (2011). 10.1126/scitranslmed.3002254
[15]
US National Library of Medicine. ClinicalTrials.gov[online], (2013).
[16]
US National Library of Medicine. ClinicalTrials.gov[online], (2013).
[17]
Dodel, R. et al. Intravenous immunoglobulin for treatment of mild-to-moderate Alzheimer's disease: a phase 2, randomized, double-blind, placebo-controlled, dose-finding trial. Lancet Neurol. 12, 233–243 (2013). 10.1016/s1474-4422(13)70014-0
[18]
Buttini, M. et al. Beta-amyloid immunotherapy prevents synaptic degeneration in a mouse model of Alzheimer's disease. J. Neurosci. 40, 9096–9101 (2005). 10.1523/jneurosci.1697-05.2005
[19]
Gilman, S. M., Koller, M. & Black, R. S. Clinical effects of Aβ immunization (AN1792) in patients with AD in an interrupted trial. Neurology 64, 1553–1562 (2005). 10.1212/01.wnl.0000159740.16984.3c
[20]
Boche, D., Denham, N., Holmes, C. & Nicoll, J. A. Neuropathology after active Aβ42 immunotherapy: implications for Alzheimer's disease pathogenesis. Acta Neuropathol. 120, 369–384 (2010). 10.1007/s00401-010-0719-5
[21]
Bard, F. et al. Peripherally administered antibodies against amyloid β-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease. Nat. Med. 6, 916–919 (2000). 10.1038/78682
[22]
Rinne, J. O. et al. 11C-PIB PET assessment of change in fibrillar amyloid-beta load in patients with Alzheimer's disease treated with bapineuzumab: a phase 2, double-blind, placebo-controlled, ascending-dose study. Lancet Neurol. 4, 363–372 (2010). 10.1016/s1474-4422(10)70043-0
[23]
Blennow, K. et al. Effect of immunotherapy with bapineuzumab on cerebrospinal fluid biomarkers levels in patients with mild to moderate Alzheimer disease. Arch. Neurol. 69, 1002–1010 (2012). 10.1001/archneurol.2012.90
[24]
Business Wire. Pfizer announces topline results of first of four studies in bapineuzumab phase 3 program. Business Wire[online], (2012).
[25]
Samadi, H. & Sultzer, D. Solanezumab for Alzheimer's disease. Expert Opin. Biol. Ther. 11, 787–798 (2011). 10.1517/14712598.2011.578573
[26]
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
[27]
Eli Lilly and Company. Lilly announces detailed results of phase 3 Solanezumab EXPEDITIONS studies following a presentation of the independent analyses by the Alzheimer's Disease Cooperative Study (ADCS). Eli Lilly and Company[online], (2012).
[28]
Tariot, P. N. Maintaining cognitive function in Alzheimer disease: how effective are current treatments? Alzheimer Dis. Assoc. Disord. 15 (Suppl. 1), S26–S33 (2001). 10.1097/00002093-200108001-00005
[29]
Giacobini, E. In The Brain Cholinergic System (eds Giacobini, E. & Pepeu, G. C.) 235–264 (Informa HealthCare, 2006). 10.1201/b14486
[30]
Mullane, K. & Williams, M. Alzheimer's therapeutics: continued clinical failures question the validity of the amyloid hypothesis—but what lies beyond? Biochem. Pharmacol. 85, 289–305 (2013). 10.1016/j.bcp.2012.11.014
[31]
Aisen, P. S. et al. Tramiprosate in mild-to-moderate Alzheimer's disease—a randomized, double-blind, placebo-controlled, multi-centre study (the Alphase Study). Arch. Med. Sci. 7, 102–111 (2011). 10.5114/aoms.2011.20612
[32]
Lannfelt, L. et al. Safety, efficacy, and biomarker findings of PBT2 in targeting Aβ as a modifying therapy for Alzheimer's disease: a phase IIa, double-blind, randomised, placebo-controlled trial. Lancet Neurol. 9, 779–786 (2008). 10.1016/s1474-4422(08)70167-4
[33]
Salloway, S. et al. A phase 2 randomized trial of ELND005, scyllo-inositol, in mild to moderate Alzheimer Disease. Neurology 77, 1253–1262 (2011). 10.1212/wnl.0b013e3182309fa5
[34]
Walker, J. R. et al. Enhanced proteolytic clearance of plasma Aβ by peripherally administered neprilysin does not result in reduced levels of brain Aβ in mice. J. Neurosci. 33, 2457–2464 (2013). 10.1523/jneurosci.3407-12.2013
[35]
Arriagada, P. V., Growdon, J. H., Hedley-White, E. T. & Hyman, B. T. Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease. Neurology 42, 631–639 (1992). 10.1212/wnl.42.3.631
[36]
Giannakopoulos, P. et al. Tangle and neuron numbers, but not amyloid load, predict cognitive status in Alzheimer's disease. Neurology 60, 1495–1500 (2003). 10.1212/01.wnl.0000063311.58879.01
[37]
Gold, G. et al. Clinical validity of Aβ-protein deposition staging in brain aging and Alzheimer disease. J. Neuropathol. Exp. Neurol. 60, 946–952 (2001). 10.1093/jnen/60.10.946
[38]
Gold, G. et al. Clinical validity of Braak neuropathological staging in the oldest-old. Acta Neuropathol. 99, 579–582 (2000). 10.1007/s004010051163
[39]
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
[40]
Pievani, M., de Haan, W., Wu, T., Seeley, W. W. & Frisoni, G. B. Functional network disruption in degenerative dementias. Lancet Neurol. 10, 829–843 (2011). 10.1016/s1474-4422(11)70158-2
[41]
LaFerla, F. M. & Green, K. N. Animal models of Alzheimer disease. Cold Spring Harb. Perspect. Med. 2, a006320 (2012). 10.1101/cshperspect.a006320
[42]
Desikan, R. S. et al. Amyloid-β-associated clinical decline occurs only in the presence of elevated P-tau. Arch. Neurol. 69, 700–713 (2012). 10.1001/archneurol.2011.3354
[43]
Corrada, M. M., Berlau, D. & Kawas, C. H. A population-based clinicopathological study in the oldest-old: the 90+ Study. Curr. Alzheimer Res. 9, 709–716 (2012). 10.2174/156720512801322537
[44]
Balasubramanian, A. B. et al. Alzheimer disease pathology and longitudinal cognitive performance in the oldest-old with no dementia. Neurol. 79, 915–921 (2012). 10.1212/wnl.0b013e318266fc77
[45]
Jack, C. R. Jr et al. Brain β-amyloid load approaches a plateau. Neurology 80, 890–896 (2013). 10.1212/wnl.0b013e3182840bbe
[46]
Villemagne, V. L. et al. Amyloid-β deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer's disease: a prospective study. Lancet Neurol. 12, 357–367 (2013). 10.1016/s1474-4422(13)70044-9
[47]
Doré, V. et al. Cross-sectional and longitudinal analysis of the relationship between Aβ deposition, cortical thickness, and memory in cognitively unimpaired individuals and in Alzheimer's disease. JAMA Neurol. 27, 1–9 (2013).
[48]
Knopman, D. S. et al. Brain injury biomarkers are not dependent on β-amyloid in normal elderly. Ann. Neurol. 73, 472–480 (2013). 10.1002/ana.23816
[49]
Marchant, N. L. et al. The aging brain and cognition: contribution of vascular injury and Aβ to mild cognitive dysfunction. JAMA Neurol. 70, 488–495 (2013). 10.1001/2013.jamaneurol.405
[50]
Wirth, M. et al. Alzheimer's disease neurodegenerative biomarkers are associated with decreased cognitive function but not β-amyloid in cognitively normal older individuals. J. Neurosci. 33, 5553–5556 (2013). 10.1523/jneurosci.4409-12.2013

Showing 50 of 88 references

Cited By
427
Designing nanozymes for in vivo applications

Ruofei Zhang, Bing Jiang · 2024

Nature Reviews Bioengineering
Nature Reviews Neurology
Current Neuropharmacology
Chemical Reviews
Tau-targeting therapies for Alzheimer disease

Erin E. Congdon, Einar M. Sigurdsson · 2018

Nature Reviews Neurology
International Journal of Geriatric...
Ageing Research Reviews
Immune attack: the role of inflammation in Alzheimer disease

Frank L. Heppner, Richard M. Ransohoff · 2015

Nature Reviews Neuroscience
Scientific Reports
Tau PET Imaging in Alzheimer’s Disease

Nobuyuki Okamura, Ryuichi Harada · 2014

Current Neurology and Neuroscience...
Metrics
427
Citations
88
References
Details
Published
Nov 12, 2013
Vol/Issue
9(12)
Pages
677-686
License
View
Cite This Article
Ezio Giacobini, Gabriel Gold (2013). Alzheimer disease therapy—moving from amyloid-β to tau. Nature Reviews Neurology, 9(12), 677-686. https://doi.org/10.1038/nrneurol.2013.223
Related

You May Also Like

Ageing as a risk factor for neurodegenerative disease

Yujun Hou, Xiuli Dan · 2019

2,787 citations

Neurofilaments as biomarkers in neurological disorders

Michael Khalil, Charlotte E. Teunissen · 2018

1,700 citations

The role of inflammation in epilepsy

Annamaria Vezzani, Jacqueline French · 2010

1,639 citations