Abstract
The hippocampus (HC) and adjacent gyri are implicated in dementia in several neurodegenerative disorders. To compare HC pathology among disorders, densities of ‘signature’ pathological lesions were measured at a standard location in eight brain regions of 12 disorders. Principal components analysis of the data suggested that the disorders could be divided into three groups: (1) Alzheimer’s disease (AD), Down’s syndrome (DS), sporadic Creutzfeldt–Jakob disease, and variant Creutzfeldt–Jakob disease in which either β-amyloid (Aβ) or prion protein deposits were distributed in all sectors of the HC and adjacent gyri, with high densities being recorded in the parahippocampal gyrus and subiculum; (2) Pick’s disease, sporadic frontotemporal lobar degeneration with TDP-43 immunoreactive inclusions, and neuronal intermediate filament inclusion disease in which relatively high densities of neuronal cytoplasmic inclusions were present in the dentate gyrus (DG) granule cells; and (3) Parkinson’s disease dementia, dementia with Lewy bodies, progressive supranuclear palsy, corticobasal degeneration, and multiple system atrophy in which densities of signature lesions were relatively low. Variation in density of signature lesions in DG granule cells and CA1 were the most important sources of neuropathological variation among disorders. Hence, HC and adjacent gyri are differentially affected in dementia reflecting either variation in vulnerability of hippocampal neurons to specific molecular pathologies or in the spread of pathological proteins to the HC. Information regarding the distribution of pathology could ultimately help to explain variations in different cognitive domains, such as memory, observed in various disorders.
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Acknowledgments
We thank the following for making tissue sections available for this study: Brain Bank, Institute of Psychiatry, London, UK; William Ellis (Department of Pathology, University of California, Davis, Sacramento, CA, USA), Ronald L. Hamilton (Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA), Ian R. A. Mackenzie (Department of Pathology, Vancouver General Hospital, Vancouver, Canada), E. Tessa Hedley-Whyte (Massachusetts General Hospital and Harvard Brain Tissue Resource Center, Belmont, MA, USA), Marla Gearing (Center for Neurodegenerative Disease, Emory University, Atlanta, GA, USA), R. H. Perry (Department of Neuropathology, Newcastle General Hospital, Newcastle-upon-Tyne, NE4 6BE, UK), C. Duyckaerts (Laboratoire de Neuropathologie, Hôpital de la Salpêtrière, Paris, France), F. Cruz-Sanchez (Institute of Neurological and Gerontological Sciences, International University of Catalonia, Barcelona, Spain), K. Skullerud (Department of Pathology, Rikshospitalet, Oslo, Norway), E. Bigio (Department of Pathology, Northwestern University Medical School, Chicago, IL, USA), and H. Yokoo (Department of Pathology, Gunma University School of Medicine, Maebashi, Japan).
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Informed consent was given for the removal of all brain tissue subject to local ethical committee approval and the 1996 Declaration of Helsinki (as modified Edinburgh 2000). The authors report no conflicts of interest.
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Armstrong, R.A., Cairns, N.J. Comparative quantitative study of ‘signature’ pathological lesions in the hippocampus and adjacent gyri of 12 neurodegenerative disorders. J Neural Transm 122, 1355–1367 (2015). https://doi.org/10.1007/s00702-015-1402-8
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DOI: https://doi.org/10.1007/s00702-015-1402-8