We postulate that preclinical Alzheimer's disease (AD) is characterized by a long asymptomatic period in which the accumulation of cerebral lesions eventually results in dementia. To be truly effective, therapeutic interventions for AD may need to be initiated in this preclinical stage, prior to the occurrence of extensive and irreversible brain image. Because preclinical AD is asymptomatic, antecedent biological markers, neuroimaging measures, or other indicators need to be developed for its antemortem identification. ? ? In this application, we test the hypothesis that biomarkers and other indicators of the cerebral changes of preclinical AD can be detected in middle age individuals, particularly those who are at increased risk for AD. We will recruit, assess, and follow two groups of adult children: those with a biologic parent with dementia of the Alzheimer type (DAT) and those for whom neither parent has DAT. Four integrated projects, supported by Administration and Clinical Cores, will evaluate antecedent biomarkers in this Adult Children Study (ACS). Project 1 will compare cerebral binding of the amyloid imaging tracer, Pittsburgh Compound B, in the 2 groups of ACS participants. Project 2 will assay markers in blood and cerebrospinal fluid (including A?, tau, and sulfatide) and conduct proteomic studies to evaluate AD risk as a function of family history and apoE genotype. Project 3 will explore attentional performance profiles, within-subject performance variability, and personality dimensions as indicators of preclinical AD. Project 4 will use structural MRI to assess volume, shape, and thickness of selected brain regions as potential neuroanatomical markers of preclinical AD. ? ? Although we appreciate that this is a high risk, high reward application, we are fully committed to the successful completion of our aims and are uniquely positioned to do so: we have demonstrated the feasibility of enrolling the ACS cohort, have an interdisciplinary team of highly accomplished investigators with a long track record of productive collaboration, and are supported by the remarkable resources and infrastructure of the Alzheimer's Disease Research Center and a complementary Program project at Washington University. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG026276-03
Application #
7253107
Study Section
Special Emphasis Panel (ZAG1-ZIJ-5 (M2))
Program Officer
Buckholtz, Neil
Project Start
2005-09-30
Project End
2010-06-30
Budget Start
2007-07-15
Budget End
2008-06-30
Support Year
3
Fiscal Year
2007
Total Cost
$1,125,950
Indirect Cost
Name
Washington University
Department
Neurology
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Roe, Catherine M; Ances, Beau M; Head, Denise et al. (2018) Incident cognitive impairment: longitudinal changes in molecular, structural and cognitive biomarkers. Brain 141:3233-3248
Ihara, Ryoko; Vincent, Benjamin D; Baxter, Michael R et al. (2018) Relative neuron loss in hippocampal sclerosis of aging and Alzheimer's disease. Ann Neurol 84:741-753
Sutphen, Courtney L; McCue, Lena; Herries, Elizabeth M et al. (2018) Longitudinal decreases in multiple cerebrospinal fluid biomarkers of neuronal injury in symptomatic late onset Alzheimer's disease. Alzheimers Dement 14:869-879
Xiong, Chengjie; Luo, Jingqin; Chen, Ling et al. (2018) Estimating diagnostic accuracy for clustered ordinal diagnostic groups in the three-class case-Application to the early diagnosis of Alzheimer disease. Stat Methods Med Res 27:701-714
Gabel, Matthew; Gooblar, Jonathan; Roe, Catherine M et al. (2018) Political Ideology, Confidence in Science, and Participation in Alzheimer Disease Research Studies. Alzheimer Dis Assoc Disord 32:179-184
Roe, Catherine M; Babulal, Ganesh M; Mishra, Shruti et al. (2018) Tau and Amyloid Positron Emission Tomography Imaging Predict Driving Performance Among Older Adults with and without Preclinical Alzheimer's Disease. J Alzheimers Dis 61:509-513
Musiek, Erik S; Bhimasani, Meghana; Zangrilli, Margaret A et al. (2018) Circadian Rest-Activity Pattern Changes in Aging and Preclinical Alzheimer Disease. JAMA Neurol 75:582-590
Aschenbrenner, Andrew J; Gordon, Brian A; Benzinger, Tammie L S et al. (2018) Influence of tau PET, amyloid PET, and hippocampal volume on cognition in Alzheimer disease. Neurology 91:e859-e866
Day, Gregory S; Gordon, Brian A; Perrin, Richard J et al. (2018) In vivo [18F]-AV-1451 tau-PET imaging in sporadic Creutzfeldt-Jakob disease. Neurology 90:e896-e906
Lewczuk, Piotr; Riederer, Peter; O'Bryant, Sid E et al. (2018) Cerebrospinal fluid and blood biomarkers for neurodegenerative dementias: An update of the Consensus of the Task Force on Biological Markers in Psychiatry of the World Federation of Societies of Biological Psychiatry. World J Biol Psychiatry 19:244-328

Showing the most recent 10 out of 352 publications