Progression of Alzheimer-type neurofibrillary tangles is related to the proximodistal segments of the hemispheric arteries.

In Alzheimer's disease (AD), neurofibrillary degeneration in the hemispheres starts in the limbic and paralimbic regions prior to those in the isocortical ones but factors determining the progression of these changes are unknown. Previous studies have shown that migration of extracellular substances (volume transmission) driven by arterial pulse pressure waves from the cerebrospinal fluid (CSF) towards the brain parenchyma occurs earlier in these limbic and paralimbic cortices located around the basal cisterns containing the proximal segments of the main hemispheric arteries than in the isocortex. Considering this similarity, the aim of our study was to examine the relation between the proximal segments of the main hemispheric arteries and the development and spread of neurofibrillary tangles (NFTs) in limbic and early isocortical Braaks' stages. Blocks following proximosdistal levels of the anterior and middle cerebral arteries containing areas of the cingulate and insular cortices, respectively, were dissected and NFTs were counted. In both regions, the density of NFTs decreased in parallel with the proximodistal segments of the accompanying arteries. Our results show that neurofibrillary degeneration in AD is related to the proximodistal levels of the main hemispheric arteries and raise the possibility that this effect is mediated by volume transmission from the CSF into the brain.

Similarities between CSF-brain extracellular transfer and neurofibrillary tangle invasion in Alzheimer's 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 Alzheimer's disease and related conditions.

Olfactory bulb in multiple system atrophy.

Olfactory dysfunction is a characteristic clinical sign in Parkinson's disease (PD); it is also present in multiple system atrophy (MSA). The pathological basis of hyposmia or anosmia in PD is well known: the olfactory bulb (OB) contains numerous Lewy bodies and severe neuronal loss is present in the anterior olfactory nucleus (AON). We established that glial cytoplasmic inclusions (GCIs) are present in all the OBs from MSA cases. Their presence in the OB is diagnostic for MSA. Additionally, neuronal loss is present in the AON in MSA. These pathological changes might be responsible for the olfactory dysfunction seen in MSA.