Mechanisms of Protein Seeding in Neurodegenerative Diseases

Figure 1. Age-associated development of neurofibrillary lesions in the dentate gyrus of mice expressing human tau selectively in the entorhinal cortex. The dentate gyrus lacks Alz50 immunoreactivity at age 12 months (A), but by age 24 months, numerous granule cells are immunopositive (B). These lesions include human tau despite the fact that human tau messenger RNA was not detectable within the cells (scale bar = 100 μm).

Figure 2. Monosynaptic and transsynaptic corticohippocampal and corticocortical connections radiating from the entorhinal cortex (EC) in young and old neuropsin-tTA-tau–transgenic mice. Young mice show accumulation of MC1-immunoreactive human tau in cell bodies and axonal tracts of the EC, the presubiculum, the parasubiculum, and projection areas (A), whereas old mice show relocation of tau to cell bodies and the appearance of human tau in synaptically connected areas in the hippocampus and neocortex (B) (scale bar = 500 μm). GC indicates granule cell layer of the dentate gyrus; H, hilus; I, inner molecular layer of the dentate gyrus; M, middle molecular layer of the dentate gyrus; O, outer molecular layer of the dentate gyrus; SLM, stratum lacunosum moleculare; SO, stratum oriens; SP, stratum pyramidale; and SR, stratum radiatum.

Figure 3. Induction of intracellular aggregation by extracellular fibrils. The C17.2 neural cells expressing a tau–yellow fluorescent protein fusion (green) (A) were exposed to recombinant fibrils labeled with AlexaFluor 546 (red) (B); in the merged image, note the colocalization of externally derived fibrils with an intracellular tau–yellow fluorescent protein inclusion, representing the induction of intracellular aggregation (C) (scale bar = 10 μm) (image courtesy of Brandon B. Holmes, BS).