Similarities between CSF–brain extracellular transfer and neurofibrillary tangle invasion in Alzheimerʹs disease

Using the in vivo enzyme protection-enzyme inhibition method, we visualized the distribution of the intraventricularly and cisternally (cisterna magna) injected ambenonium chloride (Am) bound reversibly to the extracellular acetylcholinesterase enzyme (AChE) in the rabbit brain in order to describe the extracellular flow pathways from the cerebrospinal fluid (CSF). We found that the distribution of Am-protected AChE (indicating the Am itself) is similar to tracers having no intracerebral binding sites. The topographical distribution after both ways of application indicates a preferential penetration of Am into the limbic structures of the cerebral hemispheres in a predictable topographic sequence starting from the corticoid areas, allo- and periallo cortices followed by the mesocortical regions and then, in a limited extent, to the isocortex. The lentiform nuclei and the central part of diencephalic halves are inaccessible to Am. The hierarchic order in the sequence of diffusion from the CSF into the hemispheric subpial regions and the distribution pattern of Am resemble the stereotypic topographic expansion pattern and the predominantly limbic distribution of neurofibrillary tangles (NFTs) in Alzheimerʹs disease and related conditions.