Article Figures & Data
Figures
- Fig. 1.
A, Granule cell layer of a transgene-positive 23-month-old male progeny from two F1 heterozygous APP-C100 line-seven mice. The sections are stained with toluidine blue. Note the numerous degenerating neurons in the cell layer (some indicated with white arrowheads) and in the neuropil below. Some dystrophic dendrites are evident (2800× magnification).B, Pyramidal cell layer of 28-month-old heterozygous male APP-C100 line-seven founder mouse. Note the numerous degenerating neurons in the pyramidal layer (white arrowheads). Degenerating dystrophic dendrites are also evident (arrows) (2800× magnification).
- Fig. 2.
A, Pyramidal cell layer of male 14.5-month-old Flag-APP-C100 line-one founder mouse. Observe the reduced cell density and the numerous dystrophic dendrites and degenerating neurons in the pyramidal cell layer (white arrowheads) (2800× magnification). B, Pyramidal cell layer of 14.5-month-old male Flag-APP-C100 line-17 founder mouse. Observe the degenerating neurons in the pyramidal cell layer and underlying neuropil. Degenerating dystrophic dendrites are also evident (arrows) (2800× magnification).
- Fig. 3.
A, Pyramidal cell layer of 22-month-old male C57BL/6J mouse. Note that the cell bodies are similar in size to those in B (SJL/J mouse). White arrow indicates a degenerating neuron in the pyramidal layer, but otherwise the field contains healthy neurons (2800× magnification). B, Pyramidal cell layer in 24-month-old male SJL/J mouse. Note that cell body size is similar to that shown inA, and the cells appear healthy. White arrow indicates degenerating neuron in pyramidal cell layer (2800× magnification).
- Fig. 4.
A, Neuropil of hippocampal formation of 24-month-old SJL/J male mouse. Note that the neurons are well spaced and few occur as duets with cells that appear to be glial in origin, such as those shown by the black arrows(2800× magnification). B, Neuropil of hippocampal formation of 24-month-old female APP-C100 line-seven F1 mouse. Two degenerating neurons and one healthy neuron make up this field. Observe the cytoplasmic accumulations of dense granular material that represent the aberrant secondary lysosomes that accumulate in these neurons as the mice age (black arrows). Cells adjacent to the neurons appear to have many characteristics of glial or microglial cells (star) (7000× magnification). C, Neuropil of hippocampal formation of 24-month-old female APP-C100 line-seven F1 mouse. Note the glial cells in apposition to degenerating and healthy neurons (star) and the dense cells (star) that lie close to blood vessels and resemble pericytes. Ultrastructural examination of these cells reveals that they contain degenerating debris and have a characteristic nuclear morphology that suggests they are microglial cells. Black arrows indicate the secondary lysosomal accumulations evident in the two neurons (7000× magnification).
- Fig. 5.
A, Aberrant secondary lysosomal inclusions of 28-month-old male APP-C100 line-seven F1 mouse. Note the heterogeneous granular accumulations that characterize the secondary inclusions (black arrows). Clear areas are interpreted to represent lipid-like accumulations. Observe that the cytoplasm of this reasonably healthy-looking pyramidal neuron contains whorls of membrane that may be associated in part with smooth endoplasmic reticulum (16,500× magnification). B, Secondary lysosomes in 22-month-old male C57BL/6J mouse. Note that the heterogeneous nature of the inclusions present in this mouse differs from that of the inclusions shown in A. In these inclusions (large black arrows), membranous whorls of material with few granular densities and little accumulation of lipid-like material are present. Nearby lie more typical lysosomal inclusions (small black arrows) that are much more abundant in younger normal animals of this strain (18,000× magnification). C, Secondary lysosomes in 24-month-old male SJL/J mouse. Secondary lysosomes in this mouse strain are characterized by membranous accumulations with dense heterogeneous granules within the lysosomal granule (large arrows). Nearby lie more typical lysosomal inclusions that resemble those shown in B (18,000× magnification. D, Secondary lysosomes in 14.5-month-old male line-one founder mouse. In this mouse, it is easier to find inclusions that are larger in size, but that are dense and heterogeneous, in the cytoplasm of an otherwise normal pyramidal cell (13,000× magnification). E, Secondary lysosomes in 14.5-month-old male line-17 founder mouse. Smaller inclusions than in D were found in this mouse. They have a density and heterogeneity similar to that of secondary lysosomes in aged SJL/J mice; however, vacuoles containing lipid-like material are more frequently associated with these secondary lysosomes than they are in SJL/J mice (21,600× magnification).
- Fig. 6.
A, Degenerating synapses in neuropil of 28-month-old male APP-C100 line-seven F1 mouse. Note the degenerating dendritic process in this synaptic complex (star). Also, observe whorls of membrane in cell processes, both axonal and dendritic (white arrows), and axons that contain large numbers of neurofilaments (A) (15,000× magnification). B, Degenerating neuropil from another region of the hippocampal formation of the same 28-month-old male APP-C100 line-seven F1 mouse. Again, axons with reasonable amounts of myelin contain densely packed neurofilaments (A), whorls of membrane (white arrows) are seen in dendrites (open black arrows), and a synapse in which both axonal and dendritic processes appear to be degenerating is present (star) (15,000× magnification). C, Neuropil of the underlying dentate gyrus of the hippocampal formation of the same 28-month-old male APP-C100 line-seven F1 mouse. The dentate granule cell for which the nucleus lies adjacent to the capillary contains unusual whorls of membranous material (black arrow). The densely heterochromatic nucleus with large active nucleolus that has dense cytoplasm and lies adjacent to the blood vessel as well is interpreted to be a microglial cell (M). Observe that the basement membrane of the capillary (small black arrows) is thickened and that a cell process laden with debris (black arrowhead) lies within the thickened basement membrane.
