Comparative quantitative study of ‘signature’ pathological lesions in the hippocampus and adjacent gyri of 12 neurodegenerative disorders

Richard A. Armstrong, Nigel J. Cairns

Research output: Contribution to journalArticle

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.

LanguageEnglish
Pages1355-1367
Number of pages13
JournalJournal of Neural Transmission
Volume122
Issue number10
Early online date1 May 2015
DOIs
Publication statusPublished - 2015

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Parahippocampal Gyrus
Neurodegenerative Diseases
Dementia
Hippocampus
Dentate Gyrus
Pick Disease of the Brain
Frontotemporal Lobar Degeneration
Pathology
Progressive Supranuclear Palsy
Multiple System Atrophy
Lewy Body Disease
Creutzfeldt-Jakob Syndrome
Intermediate Filaments
Molecular Pathology
Information Dissemination
Amyloid beta-Peptides
Inclusion Bodies
Cytomegalovirus Infections
Down Syndrome
Principal Component Analysis

Bibliographical note

The final publication is available at Springer via http://dx.doi.org/10.1007/s00702-015-1402-8 and http://dx.doi.org/10.1007/s00702-015-1412-6

Erratum to : Comparative quantitative study of ‘signature’ pathological lesions in the hippocampus and adjacent gyri of 12 neurodegenerative disorders. / Armstrong, Richard A.; Cairns, Nigel J. In: Journal of neural transmission, 11.06.2015.

Keywords

  • cellular inclusions
  • dentate gyrus (DG)
  • hippocampus (HC)
  • neurodegenerative disease
  • synucleinopathies
  • tauopathies

Cite this

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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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Comparative quantitative study of ‘signature’ pathological lesions in the hippocampus and adjacent gyri of 12 neurodegenerative disorders. / Armstrong, Richard A.; Cairns, Nigel J.

In: Journal of Neural Transmission, Vol. 122, No. 10, 2015, p. 1355-1367.

Research output: Contribution to journalArticle

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