Schematic representation of spirochetal invasion of the cerebral cortex reproducing the pathological hallmarks of Alzheimer's disease. Spirochetes, in an analogous way to Treponema pallidum, form argyrophilic "plaques", colonies or masses along the cerebral cortex. Accumulation of spirochetes in masses reproduces the morphology of amorphous, immature and mature plaques. Agglutination of spirochetes in the center results in a homogeneous central core, which attract microglia. Spirochetes invading neurons lead to the formation of neurofibrillary tangles, and their pleomorphic granular form to granulovacuolar degeneration. Individual spirochetes disseminate along the cerebral cortex forming neuropil threads or curly fibers. Invasion of astrocytes by spirochetes can results in a similar granular pathology as in neurons. Spirochetes can also invade microglia, which may lead to their dysfunction and diminish their capacity to fight infection. Lesions similar to plaques, tangles and granulovacuolar degeneration were all reproduced by exposure of mammalian CNS cells and organotypic cultures to spirochetes .