Figure 4.

Nuclear abnormalities in neurons in the older htau mice detected by electron microscopy suggest multiple pathways of cell death. A, B, Features of apoptosis, including nuclear breakdown, chromatin condensation, membrane blebbing, and cytoplasmic shrinkage in a 22-month-old htau mouse cortex (A) and striatum (B). Chromatin condensation into dark dispersed bodies in the absence of cell shrinkage or cell fragmentation was also detected in 22-month-old htau hippocampus (C) and cortex (D). Other neurons in the cortex (E) and thalamus (G) of htau mice displayed no prominent chromatin condensation but extensive organelle swelling and cytoplasmic vacuolization suggestive of cell lysis. Local damage, swelling, vacuolization, and demyelination were visible in axonal processes (H, I), and many of these processes contained filamentous aggregates. Neurons were also detected in the 22-month-old htau brain that had little damage (F) and displayed dispersed chromatin and intact organelles but that had accumulated aggregates. Note that the neurons that displayed nuclear breakdown did not have significant accumulations of filamentous tau (A-F). Scale bars: A-G, 2 μm; H, I, 5 μm.