Discipline: Biological Sciences
Subcategory: Physiology and Health
Session: 3
Jocelyn Ricard - University of Minnesota Twin Cities, Minneapolis, MN
Co-Author(s): An Le, University of Minnesota, Minneapolis, MN ; Sesha Krishnamachari, University of Minnesota, Minneapolis, MN ; Laura Hemmy, University of Minnesota, Minneapolis, MN ; Margaret Flanagan, University of Minnesota, Minneapolis, MN
Introduction: The Nun Study (NS) is a longitudinal study of Catholic sisters, members of the School Sisters of Notre Dame congregation, born between 1890 and 1916. With an increase in life expectancy, the oldest old is the fastest growing population in the world. Pathologic TDP-43 has been reportedly infrequently identified in the brains of cognitively intact elderly individuals, but others have described the presence of phosphorylated TDP-43 deposits in the hippocampus and/or amygdala in 36.4% of 110 non-demented aged individuals.
Hypothesis: Pathologic TDP-43 in cognitively intact aged individuals (i.e. healthy aging) is an area that requires additional study and we hypothesize the frequency of pathologic TDP will be increased in the oldest old.
Methods: Paraffin-embedded sections of brains, including bilateral posterior, middle, and anterior levels of hippocampus, amygdala, middle frontal gyrus, superior middle temporal cortex, and entorhinal from centenarians were stained. Sections of brain were screened by immunohistochemistry (IHC) for phospho-TDP-43 (clone 1D3, EMD; Millipore, Darmstadt, Germany) positive pathological inclusions. NS primary cognitive testing was done with the Consortium to Establish a Registry for AD neuropsychological battery (CERAD-NB). APOE genotyping was determined by using laboratory methods described previously. A total of 38 cases were examined and statistical analysis was performed.
Results: We found the highest frequency of pathologic TDP-43 positivity, 47.37%, in the amygdala region. Pathologic TDP-43 was associated with decreased cognitive performance overall.
Translation:
Our findings help clarify the complex relationships between pathologic TDP-43, cognitive decline, and healthy aging and further support that pathologic TDP-43 may signal pathophysiologic processes contributing to the development of cognitive impairment.
This supports the possibility that HS may act sequentially with other diseases to impair cognitive function.
Conclusion: Determination of pathologic TDP-43 prevalence in centenarians will lay the foundation for future work and may implicate their relationship to other neuropathologic lesions, cognitive function, and healthy aging in this population.
In future studies, mechanistic processes of the pathologic TDP-43 may be studied to determine the mechanisms of the progression of cognitive impairment.
Funder Acknowledgement(s): This research was supported by the National Institutes of Health?s National Center for Advancing Translational Sciences, grant UL1TR002494. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health's National Center for Advancing Translational Sciences.
Faculty Advisor: Margaret Flanagan, mflanaga@umn.edu
Role: I completed all of the IHC staining of the samples and screening. I completed literature review as well.