Figure 7

Electron microscopy and immunogold labeling of Aβ in APP23 and APP48 mice. a, b: Immunogold particles specifically labeled fibrillar Aβ (arrowheads) of a plaque in a 15-month-old APP23 mouse. At high magnification small amyloid fibrils were identified (arrowheads in b). They were located in the extracellular space. c, d: Dystrophic neurites (outlined structures) were associated with extracellular bundles of plaque-associated Aβ fibrils (arrowheads) in an 15-month-old APP23 mouse. Within the neurite, Aβ was localized in electron dense material near the surface as well as in the center of the neurite (arrows in c). d: A second dendrite without signs of dystrophy such as multilamellar bodies was also located near extracellular Aβ fibrils (outlined structure labeled with e). e: Higher magnification of this dendrite showed a dendrite cross section with an intact mitochondrium (m) and with condensed Aβ-positive material in the cytoplasm (arrows). Similar Aβ-positive material was found in the neighboring extracellular space (arrowhead). Both, intra- and extracellular Aβ aggregates did not exhibit fibrillar morphology. As such it is quite likely that these Aβ aggregates represent non-fibrillar oligomers and/or protofibrils occurring in the neighborhood of extracellular, plaque-associated Aβ fibrils. f: Fibrillar material (arrows) was observed in some dendrites of a 3-month-old APP48 mouse in an Epon-embedded, not immunostained section presumably representing the ultrastructural correlative for dendritic threads. g: Immunoelectron microscopy confirmed Aβ-positive material in fibrillar aggregates within dendritic threads labeled by gold particles (arrows) in APP48 mice. No Aβ was observed in the neighboring, non-altered mitochondrium (m). Calibration bar in g is valid for: a = 570 nm, b = 200 nm, c = 750 nm, d = 1000 nm, e = 275 nm, f, g = 350 nm.