Knight ADRC Pilots (May 2005- April 2006)
Genetic Factors Modulating Quantitative Traits in LOAD
Anthony Hinrichs, Psychiatry
Paul Kotzbauer, Neurology
Prospective Memory in DAT and APOE Genotype
Mark McDaniel, Psychology
Knight ADRC Pilots (2004-2005)
Modulation of the Metabolism of Amyloid Precursor Protein (APP) by IGF-1 Signaling Pathway
Investigator: Pang-Hsien (Benjamin) Tu, Pathology and Immunology
PET Radiotracer for Imaging Cholinergic Terminal Function in AD
Investigator: Zhude Tu, Radiology
Aging & Implicit Memory: Task Demands & Neurological Functioning
Investigator: Lisa Geraci, Psychology
Roles of Neuregulin-1 in Age-Related Neuronal Changes
Investigator: Jianxin Bao, Otolaryngology
Knight ADRC Pilots (2003-2004)
Toward a Molecular Understanding of Polyglutamine Disorders
Investigator: Rohit Pappu, Biomedical Engineering
Event Perception in Healthy Aging and Mild Dementia of the Alzheimer's Type
Investigator: Jeff Zacks, Psychology
Impact of Stroke on Psychometric Performance in Normal and Mildly Demented Individuals
Investigator: Alex Dromerick, Neurology
Acute and Chronic Effect of ß-Amyloid on Arteriolar Regulation
Investigator: Hans Dietrich, Neurosurgery
Cerebral Microhemorrhage in Patients with Alzheimer's Disease
Investigator: Jin-Moo Lee, Neurology
Role of Ubiquitination in Axonal Degeneration
Investigator: Toshiyuki Araki, Pathology & Immunology (Milbrandt Lab)
Does Repetitive Mild Traumatic Brain Injury Cause Long-Term Cognitive Impairment
Investigator: Lawrence Lewis, Emergency Medicine
Knight ADRC Pilots 2002 - 2003
Identifying compounds that delay the age-related degenerative changes in Caenorhabditis elegans
Principle Investigator: Kerry Kornfeld
Effects of the APP mutation on the brain's normal capacity for neurogenesis
Principle Investigator: John Csernansky
Molecular pathways of death in grafted dopamine neurons
Principle Investigator: Gabriel A. de Erausquin
Computerized dynamic posturography (CDP) and mildly impaired subject balance
Principle Investigator: John W. Rohrbaugh
Knight ADRC Project 2010 - 2015
Novel protein biomarkers for Alzheimer’s disease in cerebrospinal fluid
Changing tau protein levels and tau protein isoforms in mouse models of dementia
APOE metabolism in AD and controls
Knight ADRC Projects 2005 - 2010
Mapping substrate/y-secretase interactions
Project Leader: Rahpael Kopan, Ph.D.
PET Amyloid Imaging in the Elderly to Evaluate DAT Risk
Project Leader: Mark Mintun, MD
Knight ADRC Projects 2000 - 2005
Identification of Genes that Modify Age of Onset of AD
Project Leader: Alison M. Goate
CNS apolipoprotein J: Role in Aß deposition
Project Leader: David M. Holtzman
Role of LRP and its Ligand tPA in LTP and Aging
Project Leader: Guojun Bu, Ph.D.
tMRI Exploration of Memory in Aging and Early-Stage DAT
Project Leader: Randy L. Buckner
HASD Projects 2009 - 2013
Project 1 Preclinical AD predicts poststroke dementia
John C. Morris, MD
Project 2 Antecedent biomarkers of AD in CSF and plasma
David Holtzman, MD
Project 3 Markers for DAT: Control, variability, and personality
David Balota, Ph.D.
Project 4 Sequence variation in genes for biomarker proteins and age at onset
Alison Goate, DPhil
HASD Projects 2004 - 2009
Title: Informant-based dementia diagnosis in an African American community
PI: John C. Morris, MD
Hypothesis: Semi-structured informant-based interviews accurately detect the presence of dementia in African American elderly individuals in the community
1. Develop a culturally sensitive telephone version of the Memory and Aging Project Initial Subject Protocol (ISP) (collateral source interview) that is appropriate for the African American community.
2. Develop an algorithm based on responses to the collateral source interview that leads to the diagnosis of dementia.
3. Conduct telephone interviews with identified collateral sources of all consenting individuals participating in the African American Health Project, "Physical frailty in urban African Americans" (R01AG010436-07, Douglas K. Miller, PI).
4. Validate the diagnosis of dementia as derived from the collateral source interview-based algorithm.
Title: Biomarkers for pre-clinical and clinical AD
PI: David M. Holtzman, MD
Co-investigators: Anne M. Fagan, PhD; Xianlin Han, PhD
Hypothesis: The hypothesis of this proposal is that biomarkers can be developed that will assist in both predicting and improving diagnosis of early stage AD.
Utilizing both clinical and neuropsychological evaluation combined with neuropathological assessment allows one to conclude that even subjects with very mild cognitive impairment impairment can be diagnosed with Alzheimer's disease with similar sensitivity and specificity as those subjects with more advanced stages of dementia. Importantly, from neuropathological studies of elderly subjects who die when they are still cognitively normal as well as those with Down syndrome prior to the age of 40, it appears that the neuropathology of AD (plaques and tangles) appear to begin many years prior to the onset of any clinical symptoms of AD. For e.g., ~ 1/3 of subjects who die in their mid '70's while still cognitively normal, have a substantial burden of plaques and tangles (i.e. pre-clinical AD). What appears to differentiate subjects with pre-clinical AD (cognitively normal with plaques and tangles) from those with very early AD (very mildly demented with plaques and tangles) is that even the earliest clinical symptoms of AD appear to coincide with the appearance of cell loss/neuronal dysfunction in certain brain regions. Given the current issues regarding detection/prediction of AD, it would be particularly useful to develop biomarkers for AD that 1) will be useful predictors of the development of dementia of the Alzheimer type; 2) will be helpful in differentiating subjects with very mild impairment due to AD vs. other causes; and 3) will be useful in monitoring or predicting response to specific treatments. The hypothesis of this proposal is that biomarkers can be developed that will assist in both predicting and improving diagnosis of early stage AD.
1. To evaluate whether measurement of CSF sulfatides is useful as a predictive/diagnositic test for AD.
2. To evaluate whether assessment of A-beta40/A-beta42 ratio in CSF lipoproteins in CDR 0 subjects is predictive of dementia and whether the ratio is useful in diagnosis or prognosis of subjects with very mild and mild dementia.
3. To determine levels of A-beta, lipoproteins, cholesterol, and lipids in plasma, CSF, and CSF lipoproteins of individuals across the lifespan.
Title: Attention in Healthy Aging & Early Stage DAT
PI: David Balota, Ph.D.
The overall purpose of this research program is twofold: The first goal is to explore the subcomponents of attention as early indicators of DAT. This is a theoretical component of our work that continues to emphasize the role of attentional control systems in healthy aging and in early stage DAT. The second goal is to use the knowledge acquired about attentional systems to develop a research program that employs cognitive training approaches to stabilize, or increase, the cognitive functioning in early stage DAT. In addition to these goals, we will explore the moderating effects of individual differences, as reflected by psychometric performance, results from volumetric measures from the neuroimaging core, and personality measures. We believe this tripartite approach to individual differences will be critical to better understanding differences in response to training procedures.
1. Decompose subcomponents of attention (i.e., ability to sustain, select, divide, and switch attention) as potential early indicators of the onset of DAT.
2. Examine the relationship between attentional salience and memory encoding (i.e., the extent to which novel stimuli capture attention and fine tune encoding operations to increase memory performance).
3. Develop training protocols for attention and memory processing in early stage DAT. This work will depend in part on our knowledge of aspects of cognitive performance in these individuals.
HASD Projects 1998 - 2003
Intellect and Alzheimer changes in the very old
Project Leader: John C. Morris
Mapping of Neuropathology in Healthy Aging and Dementia
Project Leader: Joseph L. Price
Frontal Control Systems and Memory in Aging and DAT
Project Leader: David A. Balota
Imaging Neuronal Loss with MRI/MRS in DAT and Controls
Project Leader: Benjamin Lee