The overall objective of the Neuropathology Core of the University of Kentucky Alzheimer's Disease Center (UK-ADC) is to support research on normal brain aging, presymptomatic Alzheimer's disease (pAD), mild cognitive impairment (MCI), early and late AD, mixed dementia syndromes, and other dementing disorders. Autopsies will be performed by our Rapid Autopsy Team on longitudinally followed subjects from our Clinical Core. We will perform short post-mortem interval autopsies in relation to our clinical cohort, and we will maintain a high autopsy rate. This Core is optimally tailored to help address important research questions. The Core will provide brain tissue specimens, CSF and synaptosomes for investigators at UK, other ADCs, and outside investigators. The Core will also provide consensus conference determined diagnoses, quantitation of neurofibrillary tangles (NFT), neuritic plaques, and diffuse plaques from 8 brain regions, AB 1-40 and 1-42 quantitation, Braak staging, CERAD, and NIA-Reagan Institute staging on all autopsied cases to investigators. Since the brain bank has been operating continuously for over two decades with a strong track record, special care will be taken to ensure diagnostic excellence, consistency, and continuity. The Core will maintain a tissue bank of the above specimens and frozen serum, plasma, buffy coats and CSF from living patients. Special emphasis will be placed on defining the neuropathological findings in the brains of the oldest old (>85 years), and providing investigators with specimens from cognitively intact control subjects with no AB deposition and sparse tau pathology (successful cerebral aging) and also cognitively intact subjects with abundant plaques and neurofibrillary tangles. Providing these samples will contribute to clinical-pathological correlation studies and cutting-edge research that include sponsored studies related to AD genomics, oxidative stress, hippocampal sclerosis, dementia with Lewy bodies, amyloid precursor protein processing, Down syndrome, and neuroinflammation. Frequent consensus conferences will be held with the Clinical Core and Biostatistics Core to help define clinicalpathological diagnoses on all autopsied subjects. This Core is strongly integrated with other Cores of the UK-ADC, and exploits unique opportunities to conduct clinical-pathological correlative studies on longitudinally followed subjects. Through these methods we will better understand normal brain aging and the transition to dementia with the focused goal of contributing to therapeutic or preventive measures.

Public Health Relevance

The Neuropathology Core complements the other Cores of the University of Kentucky Alzheimer's Disease Center to provide extremely essential diagnoses and tissue samples that are required for many cutting-edge researchers at the University of Kentucky and elsewhere. We will build on our track record of excellence using innovative tools related to brain autopsies, neuropathological diagnoses, tissue banking, and state-of the-art clinical-pathological correlation.

Agency
National Institute of Health (NIH)
Type
Center Core Grants (P30)
Project #
5P30AG028383-09
Application #
8690717
Study Section
Special Emphasis Panel (ZAG1)
Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Kentucky
Department
Type
DUNS #
City
Lexington
State
KY
Country
United States
Zip Code
40506
Perez, Sylvia E; He, Bin; Nadeem, Muhammad et al. (2015) Resilience of precuneus neurotrophic signaling pathways despite amyloid pathology in prodromal Alzheimer's disease. Biol Psychiatry 77:693-703
Segerstrom, Suzanne C; Eisenlohr-Moul, Tory A; Evans, Daniel R et al. (2015) Repetitive thought dimensions, psychological well-being, and perceived growth in older adults: a multilevel, prospective study. Anxiety Stress Coping 28:287-302
Powell, David; Caban-Holt, Allison; Jicha, Gregory et al. (2014) Frontal white matter integrity in adults with Down syndrome with and without dementia. Neurobiol Aging 35:1562-9
Brenowitz, Willa D; Monsell, Sarah E; Schmitt, Frederick A et al. (2014) Hippocampal sclerosis of aging is a key Alzheimer's disease mimic: clinical-pathologic correlations and comparisons with both alzheimer's disease and non-tauopathic frontotemporal lobar degeneration. J Alzheimers Dis 39:691-702
Nelson, Peter T; Estus, Steven; Abner, Erin L et al. (2014) ABCC9 gene polymorphism is associated with hippocampal sclerosis of aging pathology. Acta Neuropathol 127:825-43
Matveev, Sergey V; Spielmann, Hans Peter; Metts, Brittney M et al. (2014) A distinct subfraction of A? is responsible for the high-affinity Pittsburgh compound B-binding site in Alzheimer's disease brain. J Neurochem 131:356-68
Weekman, Erica M; Sudduth, Tiffany L; Abner, Erin L et al. (2014) Transition from an M1 to a mixed neuroinflammatory phenotype increases amyloid deposition in APP/PS1 transgenic mice. J Neuroinflammation 11:127
Parikh, Ishita; Medway, Christopher; Younkin, Steven et al. (2014) An intronic PICALM polymorphism, rs588076, is associated with allelic expression of a PICALM isoform. Mol Neurodegener 9:32
Bradley-Whitman, Melissa A; Timmons, Michael D; Beckett, Tina L et al. (2014) Nucleic acid oxidation: an early feature of Alzheimer's disease. J Neurochem 128:294-304
Kryscio, Richard J; Abner, Erin L; Cooper, Gregory E et al. (2014) Self-reported memory complaints: implications from a longitudinal cohort with autopsies. Neurology 83:1359-65

Showing the most recent 10 out of 143 publications