This proposal is for a 5 year renewal (years 16-20) of the Alzheimer's Disease Cooperative Study (ADCS). This consortium of 34 members'sites and 46-56 participating sites is proposing both continued instrument development as well as new clinical drug studies. Instrument development will focus on innovative methods of home based assessments for a broad cohort of normal elderly(over age 75) who may have significant co-morbidities in a simulated primary prevention trial employing mail-in questionnaires, automated telephone technology and computerized data collection to assess cognitive, functional, affective, global, quality of life, and resource use measures in the home environment. The ADCS has assembled its most exciting portfolio of clinical drug trials by seeking new and innovative compounds form the biotechnology sector, individual investigator laboratories as well as from its own members. We are proposing 3 phase 3 efficacy trials of agents designed to slow progression of AD: (1) TTP488, a small novel molecule that binds to and inhibits the receptor for advanced glycation end products (RAGE) which blocks deposition of A?, (2) NAP, a novel eight amino acid peptide derived from the sequence of activity dependent neuroprotective protein(ADNP), the most potent neuroprotectant molecule currently known and (3) docosahexaenoic acid (DHA), an omega-3 fatty acid with anti-amyloid, anti-oxidant, and neuroprotectant effects. Two biomarker trials are proposed to determine if molecules of interest can produce a measurable biological signal for consideration for future efficacy trials: (1) Li, a molecule that blocks phosphorylation of tau protein and (2) resveratrol, a polyphenol derived from plants and red wine that retards the age-dependent deposition and accumulation of CNS A? and amyloid plaques. Finally, we will test the ability of passive immunization using Mg which contains natural anti-amyloid antibodies and has been demonstrated to improve cognition in early clinical trials in AD. Our existing minority recruitment core is being expanded into a general recruitment core focused on maximizing the recruitment of minorities and other subjects into our clinical trials.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AG010483-19
Application #
7643146
Study Section
Special Emphasis Panel (ZAG1-ZIJ-7 (M2))
Program Officer
Ryan, Laurie M
Project Start
1997-07-01
Project End
2012-06-30
Budget Start
2009-08-01
Budget End
2010-06-30
Support Year
19
Fiscal Year
2009
Total Cost
$9,638,092
Indirect Cost
Name
University of California San Diego
Department
Neurosciences
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Rockenstein, Edward; Ostroff, Gary; Dikengil, Fusun et al. (2018) Combined Active Humoral and Cellular Immunization Approaches for the Treatment of Synucleinopathies. J Neurosci 38:1000-1014
Edmonds, Emily C; Ard, M Colin; Edland, Steven D et al. (2018) Unmasking the benefits of donepezil via psychometrically precise identification of mild cognitive impairment: A secondary analysis of the ADCS vitamin E and donepezil in MCI study. Alzheimers Dement (N Y) 4:11-18
Chen, Yun-Fei; Ni, Xiao; Fleisher, Adam S et al. (2018) A simulation study comparing slope model with mixed-model repeated measure to assess cognitive data in clinical trials of Alzheimer's disease. Alzheimers Dement (N Y) 4:46-53
El-Agnaf, Omar; Overk, Cassia; Rockenstein, Edward et al. (2017) Differential effects of immunotherapy with antibodies targeting ?-synuclein oligomers and fibrils in a transgenic model of synucleinopathy. Neurobiol Dis 104:85-96
Jun, Gyungah R; Chung, Jaeyoon; Mez, Jesse et al. (2017) Transethnic genome-wide scan identifies novel Alzheimer's disease loci. Alzheimers Dement 13:727-738
Tarrant, Sarah D; Bardach, Shoshana H; Bates, Kendra et al. (2017) The Effectiveness of Small-group Community-based Information Sessions on Clinical Trial Recruitment for Secondary Prevention of Alzheimer's Disease. Alzheimer Dis Assoc Disord 31:141-145
Kennedy, Richard E; Cutter, Gary R; Wang, Guoqiao et al. (2017) Challenging Assumptions About African American Participation in Alzheimer Disease Trials. Am J Geriatr Psychiatry 25:1150-1159
Sokolow, Sophie; Li, Xiaohui; Chen, Lucia et al. (2017) Deleterious Effect of Butyrylcholinesterase K-Variant in Donepezil Treatment of Mild Cognitive Impairment. J Alzheimers Dis 56:229-237
Spencer, Brian; Valera, Elvira; Rockenstein, Edward et al. (2017) Anti-?-synuclein immunotherapy reduces ?-synuclein propagation in the axon and degeneration in a combined viral vector and transgenic model of synucleinopathy. Acta Neuropathol Commun 5:7
Jacobs, Diane M; Ard, M Colin; Salmon, David P et al. (2017) Potential implications of practice effects in Alzheimer's disease prevention trials. Alzheimers Dement (N Y) 3:531-535

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