title: Alzheimer's disease therapeutic research: the path forward.
abstract: The field of Alzheimer's disease therapeutic research seems poised to bring to clinic the next generation of treatments, moving beyond symptomatic benefits to modification of the underlying neurobiology of the disease. But a series of recent trials has had disappointingly negative results that raise questions about our drug development strategies. Consideration of ongoing programs demonstrates difficult pitfalls. But a clear path forward is emerging. Successful strategies will utilize newly available tools to reconsider issues of diagnosis, assessment and analysis, facilitating the study of new treatments at early stages in the disease process at which they are most likely to yield major clinical benefits.
authors.affiliation: Department of Neurosciences, University of California San Diego, Gilman Drive, La Jolla, CA 92093, USA. paisen@ucsd.edu.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Aisen
references.citation: Neurobiol Dis. 1996 Feb;3(1):16-32
references.pmid: 9173910
references.citation: Nature. 1999 Jul 8;400(6740):173-7
references.pmid: 10408445
references.citation: Nat Med. 2005 May;11(5):551-5
references.pmid: 15852017
references.citation: Ann Neurol. 2006 Mar;59(3):512-9
references.pmid: 16372280
references.citation: Neurobiol Aging. 2007 Apr;28(4):537-47
references.pmid: 16675063
references.citation: Nat Med. 2008 Sep;14(9):894
references.pmid: 18776868
references.citation: Expert Rev Neurother. 2007 Nov;7(11):1527-33
references.pmid: 17997701
references.citation: Nat Med. 2006 Jul;12(7):801-8
references.pmid: 16767098
references.citation: Lancet. 2008 Jul 19;372(9634):207-15
references.pmid: 18640457
references.citation: Nature. 2009 Feb 26;457(7233):1128-32
references.pmid: 19242475
references.citation: J Neuropathol Exp Neurol. 1999 Apr;58(4):376-88
references.pmid: 10218633
references.citation: Br Med Bull. 1996 Jul;52(3):575-86
references.pmid: 8949258
references.citation: Br J Radiol. 2007 Dec;80 Spec No 2:S92-8
references.pmid: 18445749
references.citation: Lancet. 2008 Jul 19;372(9634):216-23
references.pmid: 18640458
references.citation: N Engl J Med. 2005 Jun 9;352(23):2379-88
references.pmid: 15829527
references.citation: Alzheimers Dement. 2008 Jan;4(1):38-48
references.pmid: 18631949
references.citation: Ann Neurol. 2008 Nov;64(5):492-8
references.pmid: 19067364
references.citation: J Alzheimers Dis. 2008 Oct;15(2):289-301
references.pmid: 18953115
references.citation: Arch Neurol. 2008 Nov;65(11):1509-17
references.pmid: 19001171
references.citation: Nature. 2001 Nov 8;414(6860):212-6
references.pmid: 11700559
references.citation: CNS Spectr. 2008 Oct;13(10 Suppl 16):39-41
references.pmid: 18955962
references.citation: Lancet Neurol. 2007 Aug;6(8):734-46
references.pmid: 17616482
references.citation: BMC Neurosci. 2007 Jul 24;8:54
references.pmid: 17650315
references.citation: J Neurol Neurosurg Psychiatry. 2006 Apr;77(4):429-38
references.pmid: 16306154
references.citation: Science. 2002 Jul 19;297(5580):353-6
references.pmid: 12130773
references.citation: Nature. 1996 Aug 22;382(6593):685-91
references.pmid: 8751438
references.citation: Neurology. 2006 Nov 28;67(10):1757-63
references.pmid: 17082468
references.citation: Exp Neurol. 1998 Apr;150(2):296-304
references.pmid: 9527899
references.citation: Lancet Neurol. 2008 Jun;7(6):483-93
references.pmid: 18450517
references.citation: Neurology. 1984 Jul;34(7):939-44
references.pmid: 6610841
references.citation: Biochim Biophys Acta. 2000 Dec 20;1498(2-3):99-111
references.pmid: 11108954
references.citation: Arch Neurol. 2007 Mar;64(3):343-9
references.pmid: 17210801
references.citation: Arch Neurol. 1976 Apr;33(4):217-8
references.pmid: 1259639