The numbers and distribution of the neurofibrillary tangles and neuritic plaques have been determined in several areas of the neocortex in brains affected by various degrees of severity of Alzheimer disease. The homotypical cortex of the "association" areas of the temporal, parietal, and frontal lobes are severely involved, whereas the motor, somatic sensory, and primary visual areas are virtually unaffected. The neurofibrillary tangles are mainly in the supra-and infragranular layers, particularly in layers Ill and V. In all areas except area 18 in the occipital lobe, there are approximately twice as many tangles in layer V as in layer III. The tangles are arranged in definite clusters, and those in the supra-and infragranular layers are in register. The neuritic plaques occur in all layers but predominantly affect layers II and Ill and do not show clustering. These data on the severity of the pathological involvement in different areas of the neocortex and the laminar distribution and the clustering of the tangles support the suggestion that the pathological changes in Alzheimer disease affect regions that are interconnected by well-defined groups of connections and that the disease process may extend along the connecting fibers. The invariable and severe involvement of the olfactory areas of the brain in this disease is in striking contrast to the minimal changes in the somatic sensory and primary visual areas and raises the possibility that the olfactory pathway may be initially involved.
The number of neuronal cell bodies has been counted in a narrow strip (30 micrometers) through the depth of the neocortex in several different functional areas (motor, somatic sensory, area 17, frontal, parietal and temporal and in many species (mouse, rat, cat, monkey and man). With the exception of area 17 of the visual cortex in a number of primates the same absolute number (congruent to 110) of neurons has been found in all areas and in all species. In the binocular part of area 17 of the primates there are approximately 2.5 times more neurons. Thus in mammalian evolution the area of the neocortex increases in larger brains but the number of neurons through the depth remains constant, except in area 17 of primates. From these and other findings it is suggested that the intrinsic structure of the neocortex is basically more uniform than has been thought and that differences in cytoarchitecture and function reflect differences in connections.
The caudate nucleus of the cat appears to be homogeneous when examined with the light or electron microscope, except for a layer beneath the ependyma where there is a high concentration of glial cells and few neurons. In sections of brains stained with thionin the nerve cells in the caudate nucleus fall into three size groups: less than 8 μm, 9 to 18 μm, greater than 20 μm. Examination of material impregnated with the Golgi technique shows that there are six cell types (one small, four medium and one large), and these are distinguishable on the basis of the size of the cell somata and the appearance and arrangement of their dendrites. One type of medium cell with many dendritic spines forms over 95 % of the cell population. The large and one medium cell type are tentatively identified as the source of the efferent fibres of the nucleus. These efferent fibres and the axons of the remaining medium cell types have collateral branches. Three groups of possible afferent fibres have been identified, and these and the collateral branches of the intrinsic neurons form a dense plexus whose individual fibres cross dendrites rather than lie parallel to them. Six cell types may also be distinguished with the electron microscope, and four of these can be correlated directly with those seen in Golgi impregnated material. Several kinds of dendrites are present, the commonest having numerous spines. Fewer spines are present on other varieties of dendrite, and those dendrites which are varicose have no spines. Numerous fine, nonmyelinated axons are present.
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