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.