Skip to main content
SpringerLink
Log in

Alzheimer’s Disease Clinical Trials: Changing the Paradigm

  • Invited Commentary
  • Published:
Current Psychiatry Reports Aims and scope Submit manuscript

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

References

  1. Alzheimer’s Association: 2010. Alzheimer’s disease facts and figures. Alzheimers Dement. 2010;6(2):158–94.

    Article  Google Scholar 

  2. Phrma. Medicines in development for Alzheimer’s disease. Phrma Report (2010).

  3. Cummings J. What can be inferred from the interruption of the semagacestat trial for treatment of Alzheimer’s disease? Biol Psychiatry. 2010;68(10):876–8.

    Article  PubMed  Google Scholar 

  4. Miller G. Is pharma running out of brainy ideas? Science. 2010;329(5991):502–4.

    Article  PubMed  CAS  Google Scholar 

  5. Salloway S, Sperling R, Gilman S, Fox NC, Blennow K, Raskind M, et al. A phase 2 multiple ascending dose trial of bapineuzumab in mild to moderate Alzheimer disease. Neurology. 2009;73(24):2061–70.

    Article  PubMed  CAS  Google Scholar 

  6. Blom ES, Giedraitis V, Zetterberg H, Fukumoto H, Blennow K, Hyman BT. Rapid progression from mild cognitive impairment to Alzheimer’s disease in subjects with elevated levels of tau in cerebrospinal fluid and the APOE epsilon4/epsilon4 genotype. Dement Geriatr Cogn Disord. 2009;27(5):458–64.

    Article  PubMed  CAS  Google Scholar 

  7. Sluimer JD, Vrenken H, Blankenstein MA, Fox NC, Scheltens P, Barkhof F, et al. Whole-brain atrophy rate in Alzheimer disease: identifying fast progressors. Neurology. 2008;70(19 Pt 2):1836–41.

    PubMed  CAS  Google Scholar 

  8. Mitchell SL, Teno JM, Kiely DK, Shaffer ML, Jones RN, Prigerson HG, et al. The clinical course of advanced dementia. N Engl J Med. 2009;361(16):1529–38.

    Article  PubMed  CAS  Google Scholar 

  9. Tiraboschi P, Hansen LA, Masliah E, Alford M, Thal LJ, Corey-Bloom J. Impact of APOE genotype on neuropathologic and neurochemical markers of Alzheimer disease. Neurology. 2004;62(11):1977–83.

    PubMed  CAS  Google Scholar 

  10. Mortimer JA, Snowdon DA, Markesbery WR. The effect of APOE-epsilon4 on dementia is mediated by Alzheimer neuropathology. Alzheimer Dis Assoc Disord. 2009;23(2):152–7.

    Article  PubMed  Google Scholar 

  11. Bateman RJ, Aisen PS, De Strooper B, Fox NC, Lemere CA, Ringman JM, et al: Autosomal-dominant Alzheimer’s disease: a review and proposal for the prevention of Alzheimer’s disease. Alzheimers. Res. Ther. 3(1), 1 (2011). [Epub ahead of print].

    Google Scholar 

  12. Reiman EM, Langbaum JB, Tariot PN. Alzheimer’s prevention initiative: a proposal to evaluate presymptomatic treatments as quickly as possible. Biomark Med. 2010;4(1):3–14.

    Article  PubMed  Google Scholar 

  13. Montine TJ, Quinn J, Kaye J, Morrow JD. F(2)-isoprostanes as biomarkers of late-onset Alzheimer’s disease. J Mol Neurosci. 2007;33(1):114–9.

    Article  PubMed  CAS  Google Scholar 

  14. Alvarez A, Cacabelos R, Sanpedro C, Garcia-Fantini M, Aleixandre M. Serum TNF-alpha levels are increased and correlate negatively with free IGF-I in Alzheimer disease. Neurobiol Aging. 2007;28(4):533–6.

    Article  PubMed  CAS  Google Scholar 

  15. Ewers M, Mielke MM, Hampel H. Blood-based biomarkers of microvascular pathology in Alzheimer’s disease. Exp Gerontol. 2010;45(1):75–9.

    Article  PubMed  CAS  Google Scholar 

  16. Lee JM, Blennow K, Andreasen N, Laterza O, Modur V, Olander J, et al. The brain injury biomarker VLP-1 is increased in the cerebrospinal fluid of Alzheimer disease patients. Clin Chem. 2008;54(10):1617–23.

    Article  PubMed  CAS  Google Scholar 

  17. Lovell MA, Lynn BC, Xiong S, Quinn JF, Kaye J, Markesbery WR. An aberrant protein complex in CSF as a biomarker of Alzheimer disease. Neurology. 2008;70(23):2212–8.

    Article  PubMed  CAS  Google Scholar 

  18. Yin GN, Lee HW, Cho JY, Suk K. Neuronal pentraxin receptor in cerebrospinal fluid as a potential biomarker for neurodegenerative diseases. Brain Res. 2009;1265:158–70.

    Article  PubMed  CAS  Google Scholar 

  19. Shaw LM, Vanderstichele H, Knapik-Czajka M, Clark CM, Aisen PS, Petersen RC, et al. Cerebrospinal fluid biomarker signature in Alzheimer’s disease neuroimaging initiative subjects. Ann Neurol. 2009;65(4):403–13.

    Article  PubMed  CAS  Google Scholar 

  20. Schofield EC, Halliday GM, Kwok J, Loy C, Double KL, Hodges JR. Low serum progranulin predicts the presence of mutations: a prospective study. J Alzheimers Dis. 2010;22(3):981–4.

    PubMed  CAS  Google Scholar 

  21. Finch N, Baker M, Crook R, Swanson K, Kuntz K, Surtees R, et al. Plasma progranulin levels predict progranulin mutation status in frontotemporal dementia patients and asymptomatic family members. Brain. 2009;132(Pt 3):583–91.

    Article  PubMed  Google Scholar 

  22. Gijselinck I, Van Broeckhoven C, Cruts M. Granulin mutations associated with frontotemporal lobar degeneration and related disorders: an update. Hum Mutat. 2008;29(12):1373–86.

    Article  PubMed  CAS  Google Scholar 

  23. Mukherjee O, Wang J, Gitcho M, Chakraverty S, Taylor-Reinwald L, Shears S, et al. Molecular characterization of novel progranulin (GRN) mutations in frontotemporal dementia. Hum Mutat. 2008;29(4):512–21.

    Article  PubMed  CAS  Google Scholar 

  24. Capell A, Liebsher S, Fellerer K, Brouwers N, Willem M, Lammich S, et al. Rescue of progranulin deficiency associated with frontotemporal lobar degeneration by alkalizing reagents and inhibition of vacuolar ATPase. J Neurosci. 2011;31(5):1885–94.

    Article  PubMed  CAS  Google Scholar 

  25. Rosen HJ, Narvaez JM, Hallam B, Kramer JH, Wyss-Coray C, Gearhart R, et al. Neuropsychological and functional measures of severity in Alzheimer disease, frontotemporal dementia, and semantic dementia. Alzheimer Dis Assoc Disord. 2004;18(4):202–7.

    PubMed  Google Scholar 

Download references

Acknowledgment

The author wishes to acknowledge Christine Moore of the Cleveland Clinic for technical assistance in manuscript preparation.

Disclosure

Dr. Cummings has served as a consultant for Abbott Laboratories, Acadia Pharmaceuticals, Acerra, Adamas Pharmaceuticals, Avid, Anavex Life Sciences Corp., Astellas Pharma US, Avanir Pharmaceuticals, Baxter, Bayer HealthCare, Bristol-Myers Squibb, Eisai Co., Elan Corp., EnVivo Pharmaceuticals, ExonHit, Forest Laboratories, General Electric, Genentech, GlaxoSmithKline, Janssen Pharmaceutica, Eli Lilly and Company, H. Lundbeck A/S, MedAvante, Medivation, Medtronic, Merck & Co., Merz Pharmaceuticals, Neurokos, Neurotrax Corp., Novartis, Pfizer, Prana Biotechnology Ltd., QR Pharma, Sonexa Therapeutics, Takeda Pharmaceutical Co., Toyama, and UBC; owns stock in Adamas Pharmaceuticals, Prana Biotechnology Ltd., Sonexa Therapeutics, MedAvante, NeuroTrax Corp., Neurokos, and QR Pharma; has served as a speaker/lecturer for Eisai Co., Forest Laboratories, Janssen Pharmaceutica, Novartis, Pfizer, and H. Lundbeck A/S; owns the copyright of the Neuropsychiatric Inventory; and has provided expert witness consultation regarding olanzapine and ropinerol.

Author information

Authors and Affiliations

  1. Cleveland Clinic Lou Ruvo Center for Brain Health, 888 West Bonneville Avenue, Las Vegas, NV, 89106, USA

    Jeffrey L. Cummings

Authors
  1. Jeffrey L. Cummings
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jeffrey L. Cummings.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cummings, J.L. Alzheimer’s Disease Clinical Trials: Changing the Paradigm. Curr Psychiatry Rep 13, 437–442 (2011). https://doi.org/10.1007/s11920-011-0234-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11920-011-0234-y

Keywords

Search

Navigation