It has long been recognized that some type of reserve can protect the nervous system from expressing injury or pathology as functional impairment or clinically diagnosed disease. The overall goal of the proposed study is to identify the structural bases of neural reserve and examine the neurobiologic mechanisms through which environmental and genetic risk factors lead to the functional consequences of aging and Alzheimer's disease. We hypothesize that redundancy of several cellular and subcellular components of the neural systems responsible for cognitive and motor function are crucial for efficient performance of these systems and thereby comprise the structural basis of neural reserve. Furthermore, we hypothesize that some risk factors lead to the clinical expression of disease by promoting the accumulation of disease pathology within selectively vulnerable neural systems, whereas other risk factors reduce the likelihood that disease pathology is expressed clinically by increasing or maintaining reserve capacity (i.e., the ability of the nervous system to tolerate pathology thereby delaying the clinical expression of Alzheimer's disease and other common diseases). To test these hypotheses, we propose a longitudinal, epidemiologic clinical-pathologic study of 1,200 older persons with a wide range of educational and lifetime experiences who agree to annual detailed clinical evaluation and brain donation after death. Identifying factors that increase or maintain neural reserve offers a new and potentially powerful method whereby the clinical signs of Alzheimer's disease and other neurodegenerative conditions can be delayed. Even relatively small reductions of risk from common disabling conditions will have a major public health impact for future generations.
| Deming, Yuetiva; Dumitrescu, Logan; Barnes, Lisa L et al. (2018) Sex-specific genetic predictors of Alzheimer's disease biomarkers. Acta Neuropathol 136:857-872 |
| Haljas, Kadri; Amare, Azmeraw T; Alizadeh, Behrooz Z et al. (2018) Bivariate Genome-Wide Association Study of Depressive Symptoms With Type 2 Diabetes and Quantitative Glycemic Traits. Psychosom Med 80:242-251 |
| Jansen, Willemijn J; Wilson, Robert S; Visser, Pieter Jelle et al. (2018) Age and the association of dementia-related pathology with trajectories of cognitive decline. Neurobiol Aging 61:138-145 |
| Tan, Chin Hong; Fan, Chun Chieh; Mormino, Elizabeth C et al. (2018) Polygenic hazard score: an enrichment marker for Alzheimer's associated amyloid and tau deposition. Acta Neuropathol 135:85-93 |
| Wilson, Robert S; Capuano, Ana W; Yu, Lei et al. (2018) Neurodegenerative disease and cognitive retest learning. Neurobiol Aging 66:122-130 |
| Kommaddi, Reddy Peera; Das, Debajyoti; Karunakaran, Smitha et al. (2018) A? mediates F-actin disassembly in dendritic spines leading to cognitive deficits in Alzheimer's disease. J Neurosci 38:1085-1099 |
| Boyle, Patricia A; Yu, Lei; Wilson, Robert S et al. (2018) Person-specific contribution of neuropathologies to cognitive loss in old age. Ann Neurol 83:74-83 |
| Arvanitakis, Zoe; Capuano, Ana W; Bennett, David A et al. (2018) Body Mass Index and Decline in Cognitive Function in Older Black and White Persons. J Gerontol A Biol Sci Med Sci 73:198-203 |
| Guo, Caiwei; Jeong, Hyun-Hwan; Hsieh, Yi-Chen et al. (2018) Tau Activates Transposable Elements in Alzheimer's Disease. Cell Rep 23:2874-2880 |
| Tasaki, Shinya; Gaiteri, Chris; Mostafavi, Sara et al. (2018) The Molecular and Neuropathological Consequences of Genetic Risk for Alzheimer's Dementia. Front Neurosci 12:699 |
Showing the most recent 10 out of 492 publications
