Skip to main content

Advertisement

SpringerLink
Log in

Opportunities and challenges in developing Alzheimer disease therapeutics

  • Review
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Abstract

Alzheimer disease (AD) is a chronic, progressive disorder with an average disease progression of 7–10 years. However, the histopathological hallmark lesions of this disease, the extracellular Aβ plaques and the intraneuronal neurofibrillary tangles, start as early as childhood in the affected individuals. AD is multifactorial and probably involves many different etiopathogenic mechanisms. Thus, while AD offers a wide window of opportunity that practically includes the whole life span of the affected individuals, and numerous therapeutic targets, the multifactorial nature of this disease also makes the selection of the therapeutic targets an immensely challenging task. In addition to β-amyloidosis and neurofibrillary degeneration, the AD brain also is compromised in its ability to regenerate by enhancing neurogenesis and neuronal plasticity. An increasing number of preclinical studies in transgenic mouse models of AD show that enhancement of neurogenesis and neuronal plasticity can reverse cognitive impairment. Development of both drugs that can inhibit neurodegeneration and drugs that can increase the regenerative capacity of the brain by enhancing neurogenesis and neuronal plasticity are required to control AD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Aberg MA, Aberg ND, Hedbacker H, Oscarsson J, Eriksson PS (2000) Peripheral infusion of IGF-I selectively induces neurogenesis in the adult rat hippocampus. J Neurosci 20:2896–2903

    PubMed  CAS  Google Scholar 

  2. Abrous DN, Wojtowics JM (2008) Neurogenesis and hippocampal memory system, in adult neurogenesis. Cold Spring Harbor Press, New York

    Google Scholar 

  3. Aimone JB, Wiles J, Gage FH (2006) Potential role for adult neurogenesis in the encoding of time in new memories. Nat Neurosci 9:723–727

    Article  PubMed  CAS  Google Scholar 

  4. Anderson MF, Aberg MA, Nilsson M, Eriksson PS (2002) Insulin-like growth factor-I and neurogenesis in the adult mammalian brain. Brain Res Dev Brain Res 134:115–122

    Article  PubMed  CAS  Google Scholar 

  5. Arriagada PV, Growdon JH, Hedley-Whyte ET, Hyman BT (1992) Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer’s disease. Neurology 42:631–639

    PubMed  CAS  Google Scholar 

  6. Belleville S, Sylvain-Roy S, de Boysson C, Menard MC (2008) Characterizing the memory changes in persons with mild cognitive impairment. Prog Brain Res 169:365–375

    Article  PubMed  Google Scholar 

  7. Bird TD (2008) Genetic aspects of Alzheimer disease. Genet Med 10:231–239

    Article  PubMed  CAS  Google Scholar 

  8. Blanchard J, Chohan MO, Li B, Liu F, Iqbal K, Grundke-Iqbal I (2010) Beneficial effect of a CNTF tetrapeptide on adult hippocampal neurogenesis, neuronal plasticity and spatial memory in mice. J Alzheimer’s Dis 21:1185–1195

    Google Scholar 

  9. Blanchard J, Wanka L, Tung YC et al (2010) Pharmacologic reversal of neurogenic and neuroplastic abnormalities and cognitive impairments without affecting Abeta and tau pathologies in 3xTg-AD mice. Acta Neuropathol 120:605–621

    Article  PubMed  CAS  Google Scholar 

  10. Blurton-Jones M, Kitazawa M, Martinez-Coria H et al (2009) Neural stem cells improve cognition via BDNF in a transgenic model of Alzheimer disease. Proc Natl Acad Sci USA 106:13594–13599

    Article  PubMed  CAS  Google Scholar 

  11. Boissonneault V, Filali M, Lessard M, Relton J, Wong G, Rivest S (2009) Powerful beneficial effects of macrophage colony-stimulating factor on beta-amyloid deposition and cognitive impairment in Alzheimer’s disease. Brain 132:1078–1092

    Article  PubMed  Google Scholar 

  12. Braak H, Braak E (1997) Frequency of stages of Alzheimer-related lesions in different age categories. Neurobiol Aging 18:351–357

    Article  PubMed  CAS  Google Scholar 

  13. Braak H, Del Tredici K (2011) The pathological process underlying Alzheimer’s disease in individuals under thirty. Acta Neuropathol 121:171–181

    Article  PubMed  Google Scholar 

  14. Cameron HA, McKay RD (1999) Restoring production of hippocampal neurons in old age. Nat Neurosci 2:894–897

    Article  PubMed  CAS  Google Scholar 

  15. Chen H, Tung YC, Li B, Iqbal K, Grundke-Iqbal I (2007) Trophic factors counteract elevated FGF-2-induced inhibition of adult neurogenesis. Neurobiol Aging 28:1148–1162

    Article  PubMed  CAS  Google Scholar 

  16. Chen ZY, Cao L, Wang LM et al (2001) Development of neurotrophic molecules for treatment of neurodegeneration. Curr Protein Pept Sci 2:261–276

    Article  PubMed  CAS  Google Scholar 

  17. Chevallier NL, Soriano S, Kang DE, Masliah E, Hu G, Koo EH (2005) Perturbed neurogenesis in the adult hippocampus associated with presenilin-1 A246E mutation. Am J Pathol 167:151–159

    Article  PubMed  CAS  Google Scholar 

  18. Chohan MO, Li B, Blanchard J et al (2011) Enhancement of dentate gyrus neurogenesis, dendritic and synaptic plasticity and memory by a neurotrophic peptide. Neurobiol Aging 32:1420–1434

    Google Scholar 

  19. Chow VW, Mattson MP, Wong PC, Gleichmann M (2010) An overview of APP processing enzymes and products. Neuromolecular Med 12:1–12

    Article  PubMed  CAS  Google Scholar 

  20. Corder EH, Saunders AM, Strittmatter WJ et al (1993) Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science 261:921–923

    Article  PubMed  CAS  Google Scholar 

  21. Crystal HA, Dickson DW, Sliwinski MJ et al (1993) Pathological markers associated with normal aging and dementia in the elderly. Ann Neurol 34:566–573

    Article  PubMed  CAS  Google Scholar 

  22. Davis S, Aldrich TH, Stahl N et al (1993) LIFR beta and gp130 as heterodimerizing signal transducers of the tripartite CNTF receptor. Science 260:1805–1808

    Article  PubMed  CAS  Google Scholar 

  23. Dawbarn D, Allen SJ (2003) Neurotrophins and neurodegeneration. Neuropathol Appl Neurobiol 29:211–230

    Article  PubMed  CAS  Google Scholar 

  24. DeKosky ST, Scheff SW (1990) Synapse loss in frontal cortex biopsies in Alzheimer’s disease: correlation with cognitive severity. Ann Neurol 27:457–464

    Article  PubMed  CAS  Google Scholar 

  25. DeKosky ST, Scheff SW, Styren SD (1996) Structural correlates of cognition in dementia: quantification and assessment of synapse change. Neurodegeneration 5:417–421

    Article  PubMed  CAS  Google Scholar 

  26. Demars M, Hu YS, Gadadhar ALazarov O (2010) Impaired neurogenesis is an early event in the etiology of familial Alzheimer’s disease in transgenic mice. J Neurosci Res 88:2103–2117

    Article  PubMed  CAS  Google Scholar 

  27. Dong H, Goico B, Martin M, Csernansky CA, Bertchume AC, sernansky JG (2004) Modulation of hippocampal cell proliferation, memory, and amyloid plaque deposition in APPsw (Tg2576) mutant mice by isolation stress. Neuroscience 127:601–609

    Article  PubMed  CAS  Google Scholar 

  28. Donovan MH, Yazdani U, Norris RD, Games D, German DC, Eisch AJ (2006) Decreased adult hippocampal neurogenesis in the PDAPP mouse model of Alzheimer’s disease. J Comp Neurol 495:70–83

    Article  PubMed  Google Scholar 

  29. Dupret D, Revest JM, Koehl M et al (2008) Spatial relational memory requires hippocampal adult neurogenesis. PLoS One 3:e1959

    Article  PubMed  Google Scholar 

  30. Durany N, Michel T, Kurt J, Cruz-Sanchez FF, Cervas-Navarro J, Riederer P (2000) Brain-derived neurotrophic factor and neurotrophin-3 levels in Alzheimer’s disease brains. Int J Dev Neurosci 18:807–813

    Article  CAS  Google Scholar 

  31. Emsley JG, Hagg T (2003) Endogenous and exogenous ciliary neurotrophic factor enhances forebrain neurogenesis in adult mice. Exp Neurol 183:298–310

    Article  PubMed  CAS  Google Scholar 

  32. Garcia P, Youssef I, Utvik JK et al (2010) Ciliary neurotrophic factor cell-based delivery prevents synaptic impairment and improves memory in mouse models of Alzheimer’s disease. J Neurosci 30:7516–7527

    Article  PubMed  CAS  Google Scholar 

  33. Glenner GG, Wong CW (1984) Alzheimer’s disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun 120:885–890

    Article  PubMed  CAS  Google Scholar 

  34. Grote HE, Hannan AJ (2007) Regulators of adult neurogenesis in the healthy and diseased brain. Clin Exp Pharmacol Physiol 34:533–545

    Article  PubMed  CAS  Google Scholar 

  35. Grundke-Iqbal I, Iqbal K, Tung YC, Quinlan M, Wisniewski HM, Binder LI (1986) Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology. Proc Natl Acad Sci USA 83:4913–4917

    Google Scholar 

  36. Hardy J, Selkoe DJ (2002) The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 297:353–356

    Article  PubMed  CAS  Google Scholar 

  37. Hardy JA, Higgins GA (1992) Alzheimer’s disease: the amyloid cascade hypothesis. Science 256:184–185

    Article  PubMed  CAS  Google Scholar 

  38. Hashimoto K, Shimizu EIyo M (2004) Critical role of brain-derived neurotrophic factor in mood disorders. Brain Res Brain Res Rev 45:104–114

    Article  PubMed  CAS  Google Scholar 

  39. Haughey NJ, Liu D, Nath A, Borchard AC, Mattson MP (2002) Disruption of neurogenesis in the subventricular zone of adult mice, and in human cortical neuronal precursor cells in culture, by amyloid beta-peptide: implications for the pathogenesis of Alzheimer’s disease. Neuromolecular Med 1:125–135

    Article  PubMed  CAS  Google Scholar 

  40. Haughey NJ, Nath A, Chan SL, Borchard AC, Rao MS, Mattson MP (2002) Disruption of neurogenesis by amyloid beta-peptide, and perturbed neural progenitor cell homeostasis, in models of Alzheimer’s disease. J Neurochem 83:1509–1524

    Article  PubMed  CAS  Google Scholar 

  41. Hock C, Heese K, Hulette C, Rosenberg C, Otten U (2000) Region-specific neurotrophin imbalances in Alzheimer disease: decreased levels of brain-derived neurotrophic factor and increased levels of nerve growth factor in hippocampus and cortical areas. Arch Neurol 57:846–851

    Article  PubMed  CAS  Google Scholar 

  42. Iqbal K, Flory M, Khatoon S et al (2005) Subgroups of Alzheimer’s disease based on cerebrospinal fluid molecular markers. Ann Neurol 58:748–757

    Article  PubMed  CAS  Google Scholar 

  43. Iqbal K, Grundke-Iqbal I (2010) Alzheimer’s disease, a multifactorial disorder seeking multitherapies. Alzheimers Dementia 6:420–424

    Article  CAS  Google Scholar 

  44. Iqbal K, Grundke-Iqbal I, Zaidi T et al (1986) Defective brain microtubule assembly in Alzheimer’s disease. Lancet 2:421–426

    Article  PubMed  CAS  Google Scholar 

  45. Jin K, Galvan V, Xie L et al (2004) Enhanced neurogenesis in Alzheimer’s disease transgenic (PDGF-APPSw, Ind) mice. Proc Natl Acad Sci USA 101:13363–13367

    Article  PubMed  CAS  Google Scholar 

  46. Jin K, Xie L, Childs J et al (2003) Cerebral neurogenesis is induced by intranasal administration of growth factors. Ann Neurol 53:405–409

    Article  PubMed  CAS  Google Scholar 

  47. Karishma KK, Herbert J (2002) Dehydroepiandrosterone (DHEA) stimulates neurogenesis in the hippocampus of the rat, promotes survival of newly formed neurons and prevents corticosterone-induced suppression. Eur J Neurosci 16:445–453

    Article  PubMed  CAS  Google Scholar 

  48. Kee N, Teixeira CM, Wang AH, Frankland PW (2007) Preferential incorporation of adult-generated granule cells into spatial memory networks in the dentate gyrus. Nat Neurosci 10:355–362

    Article  PubMed  CAS  Google Scholar 

  49. Kimura T, Hong Nguyen PT, Ho SA, Tran AH, Ono T, Nishijo H (2009) T-817MA, a neurotrophic agent, ameliorates the deficits in adult neurogenesis and spatial memory in rats infused i.c.v. with amyloid-beta peptide. Br J Pharmacol 157:451–463

    Article  PubMed  CAS  Google Scholar 

  50. Knopman DS, Parisi JE, Salviati A et al (2003) Neuropathology of cognitively normal elderly. J Neuropathol Exp Neurol 62:1087–1095

    PubMed  CAS  Google Scholar 

  51. Kordower JH, Yaping C, Maclennan AJ (1997) Ciliary neurotrophic factor receptor alpha-immunoreactivity in the monkey central nervous system. J Comp Neurol 377:365–380

    Article  PubMed  CAS  Google Scholar 

  52. Lee MY, Deller T, Kirsch M, Frotscher M, Hofmann HD (1997) Differential regulation of ciliary neurotrophic factor (CNTF) and CNTF receptor alpha expression in astrocytes and neurons of the fascia dentata after entorhinal cortex lesion. J Neurosci 17:1137–1146

    PubMed  CAS  Google Scholar 

  53. Leuner B, Gould E, Shors TJ (2006) Is there a link between adult neurogenesis and learning? Hippocampus 16:216–224

    Article  PubMed  Google Scholar 

  54. Li B, Wanka L, Blanchard J et al (2010) Neurotrophic peptides incorporating adamantane improve learning and memory, promote neurogenesis and synaptic plasticity in mice. FEBS Lett 584:3359–3365

    Article  PubMed  CAS  Google Scholar 

  55. Li B, Yamamori H, Tatebayashi Y et al (2008) Failure of neuronal maturation in Alzheimer disease dentate gyrus. J Neuropathol Exp Neurol 67:78–84

    Article  PubMed  CAS  Google Scholar 

  56. Lichtenwalner RJ, Forbes ME, Bennett SA, Lynch CD, Sonntag WE, Riddle DR (2001) Intracerebroventricular infusion of insulin-like growth factor-I ameliorates the age-related decline in hippocampal neurogenesis. Neuroscience 107:603–613

    Article  PubMed  CAS  Google Scholar 

  57. Lledo PM, Alonso M, Grubb MS (2006) Adult neurogenesis and functional plasticity in neuronal circuits. Nat Rev Neurosci 7:179–193

    Article  PubMed  CAS  Google Scholar 

  58. MacLennan AJ, Vinson EN, Marks L, McLaurin DL, Pfeifer M, Lee N (1996) Immunohistochemical localization of ciliary neurotrophic factor receptor alpha expression in the rat nervous system. J Neurosci 16:621–630

    PubMed  CAS  Google Scholar 

  59. Masliah E, Mallory M, Hansen L, DeTeresa R, Alford M, Terry R (1994) Synaptic and neuritic alterations during the progression of Alzheimer’s disease. Neurosci Lett 174:67–72

    Article  PubMed  CAS  Google Scholar 

  60. Masters CL, Simms G, Weinman NA, Multhaup G, McDonald BL, Beyreuther K (1985) Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proc Natl Acad Sci USA 82:4245–4249

    Article  PubMed  CAS  Google Scholar 

  61. Mayo W, George O, Darbra S et al (2003) Individual differences in cognitive aging: implication of pregnenolone sulfate. Prog Neurobiol 71:43–48

    Article  PubMed  CAS  Google Scholar 

  62. Molofsky AV, He S, Bydon M, Morrison SJ, Pardal R (2005) Bmi-1 promotes neural stem cell self-renewal and neural development but not mouse growth and survival by repressing the p16Ink4a and p19Arf senescence pathways. Genes Dev 19:1432–1437

    Article  PubMed  CAS  Google Scholar 

  63. Nacher J, Alonso-Llosa G, Rosell DR, McEwen BS (2003) NMDA receptor antagonist treatment increases the production of new neurons in the aged rat hippocampus. Neurobiol Aging 24:273–284

    Article  PubMed  CAS  Google Scholar 

  64. Nagahara AH, Merrill DA, Coppola G et al (2009) Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer’s disease. Nat Med 15:331–337

    Article  PubMed  CAS  Google Scholar 

  65. Nathalie P, Jean-Noel O (2008) Processing of amyloid precursor protein and amyloid peptide neurotoxicity. Curr Alzheimer Res 5:92–99

    Article  PubMed  CAS  Google Scholar 

  66. Oddo S, Caccamo A, Shepherd JD et al (2003) Triple-transgenic model of Alzheimer’s disease with plaques and tangles: intracellular Abeta and synaptic dysfunction. Neuron 39:409–421

    Article  PubMed  CAS  Google Scholar 

  67. Palop JJ, Mucke L (2010) Amyloid-beta-induced neuronal dysfunction in Alzheimer’s disease: from synapses toward neural networks. Nat Neurosci 13:812–818

    Article  PubMed  CAS  Google Scholar 

  68. Phillips W, Michell AW, Barker RA (2006) Neurogenesis in diseases of the central nervous system. Stem Cells Dev 15:359–379

    Article  PubMed  CAS  Google Scholar 

  69. Pimplikar SW, Nixon RA, Robakis NK, Shen J, Tsai LH (2010) Amyloid-independent mechanisms in Alzheimer’s disease pathogenesis. J Neurosci 30:14946–14954

    Article  PubMed  CAS  Google Scholar 

  70. Price RD, Milne SA, Sharkey J, Matsuoka N (2007) Advances in small molecules promoting neurotrophic function. Pharmacol Ther 115:292–306

    Article  PubMed  CAS  Google Scholar 

  71. Rai KS, Hattiangady B, Shetty AK (2007) Enhanced production and dendritic growth of new dentate granule cells in the middle-aged hippocampus following intracerebroventricular FGF-2 infusions. Eur J Neurosci 26:1765–1779

    Article  PubMed  Google Scholar 

  72. Rapoport M, Dawson HN, Binder LI, Vitek MP, Ferreira A (2002) Tau is essential to beta-amyloid-induced neurotoxicity. Proc Natl Acad Sci USA 99:6364–6369

    Article  PubMed  CAS  Google Scholar 

  73. Robakis NK (2010) Mechanisms of AD neurodegeneration may be independent of Abeta and its derivatives. Neurobiol Aging 32:372–379

    Google Scholar 

  74. Roberson ED, Scearce-Levie K, Palop JJ et al (2007) Reducing endogenous tau ameliorates amyloid beta-induced deficits in an Alzheimer’s disease mouse model. Science 316:750–754

    Article  PubMed  CAS  Google Scholar 

  75. Rodrigue KM, Kennedy KM, Park DC (2009) Beta-amyloid deposition and the aging brain. Neuropsychol Rev 19:436–450

    Article  PubMed  Google Scholar 

  76. Rosenblad C (2004) Growth factor treatment of neurodegenerative disorders: new developments pave the way for clinical success. IDrugs 7:243–248

    PubMed  CAS  Google Scholar 

  77. Sanchez-Ramos J, Song S, Sava V et al (2009) Granulocyte colony stimulating factor decreases brain amyloid burden and reverses cognitive impairment in Alzheimer’s mice. Neuroscience 163:55–72

    Article  PubMed  CAS  Google Scholar 

  78. Schulte-Herbruggen O, Braun A, Rochlitzer S, Jockers-Scherubl MC, Hellweg R (2007) Neurotrophic factors–a tool for therapeutic strategies in neurological, neuropsychiatric and neuroimmunological diseases? Curr Med Chem 14:2318–2329

    Article  PubMed  CAS  Google Scholar 

  79. Senaldi G, Varnum BC, Sarmiento U et al (1999) Novel neurotrophin-1/B cell-stimulating factor-3: a cytokine of the IL-6 family. Proc Natl Acad Sci USA 96:11458–11463

    Article  PubMed  CAS  Google Scholar 

  80. Sendtner M, Carroll P, Holtmann B, Hughes RA, Thoenen H (1994) Ciliary neurotrophic factor. J Neurobiol 25:1436–1453

    Article  PubMed  CAS  Google Scholar 

  81. Shi Y, Wang W, Yourey PA et al (1999) Computational EST database analysis identifies a novel member of the neuropoietic cytokine family. Biochem Biophys Res Commun 262:132–138

    Article  PubMed  CAS  Google Scholar 

  82. Terry RD, Masliah E, Salmon DP et al (1991) Physical basis of cognitive alterations in Alzheimer’s disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol 30:572–580

    Article  PubMed  CAS  Google Scholar 

  83. Trejo JL, Carro E, Torres-Aleman I (2001) Circulating insulin-like growth factor I mediates exercise-induced increases in the number of new neurons in the adult hippocampus. J Neurosci 21:1628–1634

    PubMed  CAS  Google Scholar 

  84. Tsai KJ, Tsai YC, Shen CK (2007) G-CSF rescues the memory impairment of animal models of Alzheimer’s disease. J Exp Med 204:1273–1280

    Article  PubMed  CAS  Google Scholar 

  85. Tuszynski MH, Thal L, Pay M et al (2005) A phase 1 clinical trial of nerve growth factor gene therapy for Alzheimer disease. Nat Med 11:551–555

    Article  PubMed  CAS  Google Scholar 

  86. van Praag H, Schinder AF, Christie BR, Toni N, Palmer TD, Gage FH (2002) Functional neurogenesis in the adult hippocampus. Nature 415:1030–1034

    Article  PubMed  Google Scholar 

  87. Verret L, Jankowsky JL, Xu GM, Borchelt DR, Rampon C (2007) Alzheimer’s-type amyloidosis in transgenic mice impairs survival of newborn neurons derived from adult hippocampal neurogenesis. J Neurosci 27:6771–6780

    Article  PubMed  CAS  Google Scholar 

  88. Wang JM, Singh C, Liu L et al (2010) Allopregnanolone reverses neurogenic and cognitive deficits in mouse model of Alzheimer’s disease. Proc Natl Acad Sci USA 107:6498–6503

    Article  PubMed  CAS  Google Scholar 

  89. Wang JZ, Grundke-Iqbal I, Iqbal K (2007) Kinases and phosphatases and tau sites involved in Alzheimer neurofibrillary degeneration. Eur J Neurosci 25:59–68

    Article  PubMed  Google Scholar 

  90. Wen PH, Hof PR, Chen X et al (2004) The presenilin-1 familial Alzheimer disease mutant P117L impairs neurogenesis in the hippocampus of adult mice. Exp Neurol 188:224–237

    Article  PubMed  CAS  Google Scholar 

  91. Yang P, Arnold SA, Habas A, Hetman M, Hagg T (2008) Ciliary neurotrophic factor mediates dopamine D2 receptor-induced CNS neurogenesis in adult mice. J Neurosci 28:2231–2241

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We are grateful to Janet Murphy for secretarial assistance. Studies from our lab described in this article were supported in part by NIH grants AG019158, AG028538, Alzheimer’s Association grant IIRG-06-25836, a research grant from EVER Neuropharma, Unteract, Austria, and by the New York State Office of People with Developmental Disabilities.

Author information

Authors and Affiliations

  1. Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY, 10314-6399, USA

    Khalid Iqbal & Inge Grundke-Iqbal

Authors
  1. Khalid Iqbal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Inge Grundke-Iqbal
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Khalid Iqbal.

Additional information

This article is dedicated to the celebration of Prof. Kurt Jellinger’s 80th birthday, which was on May 28th.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Iqbal, K., Grundke-Iqbal, I. Opportunities and challenges in developing Alzheimer disease therapeutics. Acta Neuropathol 122, 543–549 (2011). https://doi.org/10.1007/s00401-011-0878-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00401-011-0878-z

Keywords

Search

Navigation