Variants of arterial supply to the inferior (diaphragmatic) surface of the ventricles of the heart and the influence on age at death.

Coronary artery systems of the inferior wall of the ventricles vary considerably. Schlesinger's concept distinguishes dominance of the right or left coronary artery (LCA) or balanced type. LCA dominance has been reported to be associated with increased mortality.

The relation between tau pathology and granulovacuolar degeneration of neurons.

Neurofibrillary tangles arising from aggregated microtubule-associated protein tau occur in aged brains and are hallmarks of neurodegenerative diseases. A subset of neurons containing aggregated tau displays granulovacuolar degeneration (GVD) that is characterized by membrane-bound cytoplasmic vacuoles, each containing an electron-dense granule (GVB). Tau pathology induces GVBs in experimental models, but GVD does not generally follow tau pathology in the human brain.

Effect of tau-pathology on charged multivesicular body protein 2b (CHMP2B).

Charged multivesicular body protein 2b (CHMP2B) is a subunit of the endosomal sorting complex required for transport (ESCRT)-III that mediates scission of budded membranes. Neurons with CHMP2B-positive granulovacuolar inclusions in the cytoplasm are much more frequent in hippocampi of cases with Alzheimer's disease when compared with controls. We analyzed immunolabeled brain sections from tau-transgenic mice, APP-transgenic mice, non-transgenic mice, and human hippocampi to investigate the relation between CHMP2B and tau and plaque pathology that are major histopathological features of Alzheimer's disease.

Distribution of spleen tyrosine kinase and tau phosphorylated at tyrosine 18 in a mouse model of tauopathy and in the human hippocampus.

Purpose: Spleen tyrosine kinase (Syk) has been shown to phosphorylate tyrosine 18 of tau in vitro. It has been proposed that increased immunoreactivity for double-phosphorylated Syk in hippocampal neurons of Alzheimer's disease cases indicates a not yet defined neurodegenerative process. To investigate this possibility we have studied Syk and tau phosphorylated at tyrosine 18 (pTyr18) in transgenic mice and human hippocampi.

Analysis of ribosomal protein S6 baseline phosphorylation and effect of tau pathology in the murine brain and human hippocampus.

We examined the distribution pattern of the phosphorylated 40S ribosomal subunit protein S6, a downstream target of the mTOR pathway, in the brains of 24-months-old human tau transgenic pR5 mice, non-transgenic littermates and in human hippocampi. We studied baseline levels of phosphorylated S6 and a possible effect of tau pathology. S6 phosphorylated at Ser235/236 (pS6Ser235/236) or Ser240/244 (pS6Ser240/244) has been used as a read-out of mTOR activity in several studies.

Granulovacuolar degeneration and unfolded protein response in mouse models of tauopathy and Aβ amyloidosis.

Histopathological studies on the brains of tauopathy cases including cases with Alzheimer's disease (AD) demonstrate that neurons with hyperphosphorylated protein tau display granulovacuolar degeneration (GVD), as evidenced by vacuolar lesions harboring a central granule, together with markers of the activated unfolded protein response (UPR). In order to examine whether this hallmark is reproduced in animal models we studied the presence of GVD and the activated UPR in two complementary mouse models, pR5 mice with a tau pathology and APPSLxPS1mut mice with an amyloid plaque pathology. Neither GVD nor a significant activation of the UPR was found in both APPSLxPS1mut mice and in those regions in the pR5 brain where only neurons with an early stage of tau hyperphosphorylation were present.

Active glycogen synthase kinase-3 and tau pathology-related tyrosine phosphorylation in pR5 human tau transgenic mice.

We studied underlying pathomechanisms in tauopathies using pR5 mice that express the P301L tau mutation found in familial forms of frontotemporal dementia. In a longitudinal study we investigated the functional status of glycogen synthase kinase-3 and correlated it with the appearance of distinct tau phospho-epitopes. Neurons displaying increases in activating phosphorylation of glycogen synthase kinase-3α/β at tyrosine 279/216 also showed an intense rather than moderate AT8 (phospho-Ser202/Thr205 tau) immunoreactivity, and immunoreactivity for AT100 (phospho-Ser212/Thr214 tau) and phosphorylated Ser422, phospho-epitopes associated with fibrillar tau pathology.