Carmen Soriano Herrador

University of Castilla-La Mancha

Unraveling hippocampal subfield-specific proteomic changes during Alzheimer’s disease progression

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Biography

Hondius, D. C., van Nierop, P., Li, K. W., Hoozemans, J. J., van der Schors, R. C., van Haastert, E. S., van der Vies, S. M., Rozemuller, A. J., & Smit, A. B. (2016). Profiling the human hippocampal proteome at all pathologic stages of Alzheimer's disease. Alzheimer's & dementia : the journal of the Alzheimer's Association, 12(6), 654–668. https://doi.org/10.1016/j.jalz.2015.11.002 Braak, H., Alafuzoff, I., Arzberger, T., Kretzschmar, H., & Del Tredici, K. (2006). Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry. Acta Neuropathologica, 112(4), 389-404. https://doi.org/10.1007/s00401-006-0127-z Gonzalez-Rodriguez, M., Villar-Conde, S., Astillero-Lopez, V., Villanueva-Anguita, P., Ubeda-Banon, I., Flores-Cuadrado, A., Martinez-Marcos, A., & Saiz-Sanchez, D. (2021). Neurodegeneration and Astrogliosis in the Human CA1 Hippocampal Subfield Are Related to hsp90ab1 and bag3 in Alzheimer’s Disease. International Journal of Molecular Sciences, 23(1), 165. https://doi.org/10.3390/ijms23010165

Abstract

Alzheimer’s disease (AD) is the most widespread neurodegenerative disorder, with a higher incidence in women. Neuropathological signs of the disease include early pathological deposits of tau and amyloid-? protein, astrogliosis and neurodegeneration in the entorhino-hippocampal axis. Previous stereological and proteomic data comparing control cases with advanced AD cases (Braak stages V-VI) have demonstrated specific involvement of hippocampal subregions (cornua ammonis – CA1, CA2, CA3- and dentate gyrus -DG-) in AD, showing that CA1 is the most affected by astrogliosis and neurodegeneration. Nevertheless, proteomic analyses focused on single hippocampal subfields, paying special attention to the changes during AD progression, have not been carried out yet. This study aimed to identify the proteomic differences between the human hippocampal subfields related to the development and the progression of the Alzheimer’s disease. Fresh-frozen human hippocampal tissue blocks from female AD cases were divided in three groups: group 1, Braak stages I-II; group 2, Braak stages III-IV, and Braak stages V-VI. They were cryostatsectioned and collected on specific slides. On one hand, part of the sections was processed to perform MALDI Imaging assay to analyze the peptidic profiles from the regions of interest (ROIs): CA1, CA2, CA3 and DG. On the other hand, remaining sections were Nissl stained and the ROIs were microdissected and collected in separate tubes. Tissue extracts from microdissection were used to perform LC-MS/MS analysis to identify specific hippocampal region protein subsets. Our analysis revealed distinct proteomic profiles in the hippocampal subfields analyzed across AD stages. The proteomic analysis allowed us to identify differentially expressed proteins (DEPs) in each region during the progression of the pathology, which were characterized using the bibliography to find out the ones that could have a role as potential biomarkers. The description of the hippocampal subfields proteome and the identification of differentially expressed proteins in each hippocampal region during the progression of the pathology represent significant steps towards Alzheimer’s disease understanding.