Neurodegenerative disorders are characterized by abundant protein aggregates in brain and spinal cord (CNS) that are the defining neuropathology (NP) of these disorders as exemplified by senile plaques (SPs) and neurofibrillary tangles (NFTs), the diagnostic signatures of Alzheimer's disease (AD). However, AD is associated with Lewy bodies (LBs) and TDP-43 pathologies in >50% of patients while mild cognitive impairment (MCI) often shows abundant SPs and NFTs at autopsy consistent with AD. Further, the NP in ~25% or more of frontotemporal lobar degeneration (FTLD) patients is AD, while the remaining FTLD cases are non-AD tauopathies (FTLD-Tau), TDP-43 proteinopathy (FTLD-TDP) or, rarely, FUS proteinopathy (FTLD-FUS). Thus, a definitive diagnosis of AD and related dementias is established definitively only by postmortem NP examination, and an accurate NP diagnosis is essential for informative clinicopathologic correlations to elucidate molecular mechanisms of MCI, AD, FTLD and other dementias such as Parkinson's disease with dementia and dementia with LBs. Since multiple genetic factors contribute to the risk for AD and biomarkers signal disease onset/progression, DNA and biofluid banking is critical for genetic and biomarker studies. Hence, the University of Pennsylvania (Penn) AD Core Center (ADCC) characterizes and banks CNS tissues, DNA and biofluids from well-characterized patients followed in Clinical Core B with AD and related disorders as well as normal control subjects. This is essential for research conducted in ADCC Pilots and other grants that utilize Penn ADCC resources. Accordingly, Core D is re-named the Neuropathology, Genetics and Biomarker Core to reflect the full scope of its current activities. Core D also distributes tissue, DNA and biofluids to investigators at and beyond Penn for research. Finally, Core D works with the Data Management and Statistics Core C to enter all information into a database, maintain data confidentiality, and provide these data to NACC. In summary, Core D performs critical functions to support the mission of the Penn ADCC.

Public Health Relevance

Core D is highly relevant to the continued success of the Penn ADCC because it provides critical diagnostic, biosample banking and expertise in NP, genetics and biomarker studies that support the mission of the Penn ADCC which challenges/re-defines current clinical practice paradigms and research on AD and related disorders as well as MCI and normal aging by utilizing novel concepts and approaches to achieve the goals ofthis ADCC including integration of genetics and biomarkers with postmortem pathologic analysis.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Center Core Grants (P30)
Project #
5P30AG010124-23
Application #
8501187
Study Section
Special Emphasis Panel (ZAG1-ZIJ-5)
Project Start
Project End
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
23
Fiscal Year
2013
Total Cost
$164,619
Indirect Cost
$61,732
Name
University of Pennsylvania
Department
Type
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Wang, Hua; Stewart, Tessandra; Toledo, Jon B et al. (2018) A Longitudinal Study of Total and Phosphorylated ?-Synuclein with Other Biomarkers in Cerebrospinal Fluid of Alzheimer's Disease and Mild Cognitive Impairment. J Alzheimers Dis 61:1541-1553
Nativio, Raffaella; Donahue, Greg; Berson, Amit et al. (2018) Publisher Correction: Dysregulation of the epigenetic landscape of normal aging in Alzheimer's disease. Nat Neurosci 21:1018
Hanfelt, John J; Peng, Limin; Goldstein, Felicia C et al. (2018) Latent classes of mild cognitive impairment are associated with clinical outcomes and neuropathology: Analysis of data from the National Alzheimer's Coordinating Center. Neurobiol Dis 117:62-71
Adler, Daniel H; Wisse, Laura E M; Ittyerah, Ranjit et al. (2018) Characterizing the human hippocampus in aging and Alzheimer's disease using a computational atlas derived from ex vivo MRI and histology. Proc Natl Acad Sci U S A 115:4252-4257
Vickers, Kayci L; Breslin, Kathleen; Roalf, David R et al. (2018) Older Adult Normative Data for the Sniffin' Sticks Odor Identification Test. Arch Clin Neuropsychol :
Zhou, Zilu; Wang, Weixin; Wang, Li-San et al. (2018) Integrative DNA copy number detection and genotyping from sequencing and array-based platforms. Bioinformatics 34:2349-2355
Blue, Elizabeth E; Bis, Joshua C; Dorschner, Michael O et al. (2018) Genetic Variation in Genes Underlying Diverse Dementias May Explain a Small Proportion of Cases in the Alzheimer's Disease Sequencing Project. Dement Geriatr Cogn Disord 45:1-17
Guerreiro, Rita; Ross, Owen A; Kun-Rodrigues, Celia et al. (2018) Investigating the genetic architecture of dementia with Lewy bodies: a two-stage genome-wide association study. Lancet Neurol 17:64-74
Walsh, Ryan R; Krismer, Florian; Galpern, Wendy R et al. (2018) Recommendations of the Global Multiple System Atrophy Research Roadmap Meeting. Neurology 90:74-82
McGurk, L; Mojsilovic-Petrovic, J; Van Deerlin, V M et al. (2018) Nuclear poly(ADP-ribose) activity is a therapeutic target in amyotrophic lateral sclerosis. Acta Neuropathol Commun 6:84

Showing the most recent 10 out of 720 publications