Temporal lobe pathology in neurodegenerative disease:a comparative study of eight disorders with special reference to the hippocampus

The temporal lobe is a major site of pathology in a number of neurodegenerative diseases. In this chapter, the densities of the characteristic pathological lesions in various regions of the temporal lobe were compared in eight neurodegenerative disorders, viz., Alzheimer’s disease (AD), Down’s syndrome (DS), dementia with Lewy bodies (DLB), Pick’s disease (PiD), corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), sporadic Creutzfeldt-Jakob disease (sCJD), and neuronal intermediate filament inclusion disease (NIFID). Temporal lobe pathology was observed in all of these disorders most notably in AD, DS, PiD, sCJD, and NIFID. The regions of the temporal lobe affected by the pathology, however, varied between disorders. In AD and DS, the greatest densities of ?-amyloid (A?) deposits were recorded in cortical regions adjacent to the hippocampus (HC), DS exhibiting greater densities of A? deposits than AD. Similarly, in sCJD, greatest densities of prion protein (PrPsc) deposits were recorded in cortical areas of the temporal lobe. In AD and PiD, significant densities of neurofibrillary tangles (NFT) and Pick bodies (PB) respectively were present in sector CA1 of the HC while in CBD, the greatest densities of tau-immunoreactive neuronal cytoplasmic inclusions (NCI) were present in the parahippocampal gyrus (PHG). Particularly high densities of PB were present in the DG in PiD, whereas NFT in AD and Lewy bodies (LB) in DLB were usually absent in this region. These data confirm that the temporal lobe is an important site of pathology in the disorders studied regardless of their molecular ‘signature’. However, disorders differ in the extent to which the pathology spreads to affect the HC which may account for some of the observed differences in clinical dementia.

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

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.

Neuropathology of the sporadic and variant subtypes of Creutzfeldt-Jakob disease:a comparative quantitative study

The objective of the present study was to compare quantitatively the neuropathology of two subtypes of Creutzfeldt-Jakob disease (CJD), viz., sporadic CJD (sCJD) and variant CJD (vCJD). The vacuolation (‘spongiform change’), surviving neurons, glial cell nuclei, and deposits of the disease form of prion protein (PrPsc) were quantified in histological sections of the cerebral cortex, hippocampus, and cerebellum in 11 cases of sCJD and 15 cases of vCJD. Three aspects of the quantitative pathology of each histological feature were studied: overall abundance (density or coverage), spatial distribution parallel to the tissue boundary, and laminar distribution across gyri of the cerebral cortex. Overall vacuole density was greater in sCJD than in vCJD in some regions while overall neuronal densities were greater in vCJD. In cerebral cortex, vacuoles and PrPsc deposits were distributed in clusters which exhibited a regular distribution parallel to the pia mater, this type of spatial pattern being more frequent in sCJD than in vCJD. In some cortical gyri there were differences in laminar distribution between subtypes, viz. the vacuolation was more generally distributed across cortical laminae in sCJD, neuronal loss was often greater in upper laminae in vCJD but in lower laminae in sCJD, and PrPsc deposits were more frequently distributed in upper laminae in vCJD but in lower laminae in sCJD. A significant gliosis affected lower cortical laminae in both sCJD and vCJD. Hence, there were differences in degeneration of cerebral cortex, hippocampus, and cerebellum in sCJD and vCJD, which may reflect variations in disease aetiology and propagation of PrPsc through the brain.

Comparative quantitative neuropathology of the sporadic and variant subtypes of Creutzfeldt-Jakob disease

The objective of the present study was to compare quantitatively the neuropathology of two subtypes of Creutzfeldt-Jakob disease (CJD), viz., sporadic CJD (sCJD) and variant CJD (vCJD). The vacuolation (‘spongiform change’), surviving neurons, glial cell nuclei, and deposits of the disease form of prion protein (PrPsc) were quantified in histological sections of the cerebral cortex, hippocampus, and cerebellum in 11 cases of sCJD and 15 cases of vCJD. Three aspects of the quantitative pathology of each histological feature were studied: overall abundance (density or coverage), spatial distribution parallel to the tissue boundary, and laminar distribution across gyri of the cerebral cortex. Overall vacuole density was greater in sCJD than in vCJD in some regions while overall neuronal densities were greater in vCJD. In cerebral cortex, vacuoles and PrPsc deposits were distributed in clusters which exhibited a regular distribution parallel to the pia mater, this type of spatial pattern being more frequent in sCJD than in vCJD. In some cortical gyri there were differences in laminar distribution between subtypes, viz. the vacuolation was more generally distributed across cortical laminae in sCJD, neuronal loss was often greater in upper laminae in vCJD but in lower laminae in sCJD, and PrPsc deposits were more frequently distributed in upper laminae in vCJD but in lower laminae in sCJD. A significant gliosis affected lower cortical laminae in both sCJD and vCJD. Hence, there were differences in degeneration of cerebral cortex, hippocampus, and cerebellum in sCJD and vCJD, which may reflect variations in disease aetiology and propagation of PrPsc through the brain.