Argyrophilic tau-positive twisted and non-twisted tubules in astrocytic processes in brains of Alzheimer-type dementia: an electron microscopical study

Abstract

This report concerns pathological astrocytic tubular structures (astrocytic tubules, As-Tbs) that coexist with glial filaments in astrocytic processes in brains with presenile-onset Alzheimer-type dementia. The formation of As-Tbs appears to be related to the duration of disease and the intensity of Alzheimer histopathology. In three cases in which the disease was of extremely long duration, As-Tbs were found in the frontal and temporal neocortices, the temporal pole and the hippocampus using electron microscopy, whereas they were not found in two cases with a long, but not extremely long, illness duration. As-Tbs were almost exclusively found in the highly devastated neuropil, and we could not find them in regions of moderate neuronal degeneration despite intensive inspection. As reported previously, some As-Tbs was seen adjacent to extracellular neurofibrillary tangles (NFTs) and in perivascular astrocytes. Our novel finding is that they can exist independently from these, in the highly devastated neuropil. Two types of As-Tbs were observed, twisted tubules with periodic constrictions at 50- to 80-nm intervals and non-twisted tubules where no constrictions were seen but which had a 15-nm fuzzy outer contour. They were positively stained by anti-human tau antibody, an antibody that does not recognize extracellular NFTs. Thus, it is most likely that As-Tbs are not the sequestration of extracellular NFTs, and that they are of astrocytic origin. Moreover, As-TBs showed argyrophilia. As-TBs appear indistinguishable from dystrophic neurites under the light microscope. The present data suggest that they may be more widely distributed in the damaged cerebral neuropil than previously thought.

MRI-visible perivascular space location is associated with Alzheimer's disease independently of amyloid burden

“…Alternatively CAA may disrupt perivascular drainage via perturbations in normal arteriolar pulsation (Hawkes et al, 2014;Kress et al, 2014). It is also possible that the presence of hyper-phosphorylated tau has direct deleterious consequences for perivascular astrocytes, for example by directly disrupting their microtubular structure, or altering the expression or localisation of membrane channels (for example, aquaporin 4) that change normal interstitial fluid dynamics, with the eventual outcome of an enlarged perivascular space (Arima et al, 1998;Thrane et al, 2014;Iqbal et al, 2016).…”

Ultrastructural characteristics of tau filaments in tauopathies: Immuno‐electron microscopic demonstration of tau filaments in tauopathies

“…In AD, twisted and non-twisted tubules in astrocytic processes were demonstrated to closely resemble twisted and straight tubules in neurons. 15,16 Coiled bodies and argyrophilic threads were demonstrated to be comprised of abnormal tubules, 13-15 nm smooth tubules with fuzzy outer contours in PSP, 17 and 15-20 nm tubules with occasional constrictions in CBD, 18 both of which resemble tautubules in NFT.…”

Aging-related tau astrogliopathy (ARTAG): harmonized evaluation strategy

“…These studies, however, were limited to evaluation of the MTL and did not take account of cortical and subcortical tau astrogliopathy. Few studies reported tau immunopositivity in glial cells in AD cases with prolonged duration of the disease [5, 48, 68]. Finally, a report on NFT-dementia mentioned the presence of astrocytic tau pathology in white matter and cortex [31].…”

“…The introduction of the Gallyas silver stain and particularly diagnostic tau immunohistochemistry led to the identification of astroglial tau pathology in the aging brain in people with or without AD-related changes, cognitive decline or movement disorders [5, 7, 11, 21, 25, 31, 34–36, 38, 46, 57]. There have been attempts to classify these tau astrogliopathies [34], but there is lack of consensus as to how best to describe and categorize them.…”