Regional distribution of tau, β-amyloid and β-amyloid precursor protein in the Alzheimerʼs brain

Abstract

Regional variation in the distribution of SP and NFT within the brain is well documented. Consideration of such variation is potentially of help in formulating models of disease progression. Several models propose that pathological changes in Alzheimer's disease (AD) progress in a step-wise fashion along neuronally connected regions. In this study, we measured tau, Abeta and betaAPP load in different brain regions and examined our results against models of AD progression. Blocks of brain tissue from 45 AD and 15 control cases were immunolabelled for tau, Abeta and betaAPP. Immunolabelled areas were measured as a proportion of the area of the field. Tau load was almost twice as great in the entorhinal cortex than elsewhere in the brain and was least in the cingulate gyrus. In contrast, Abeta was greatest in the cingulate gyrus and least in the entorhinal cortex. BetaAPP rankings were similar to those of tau. Thus the site with the greatest Abeta load (cingulate cortex) had the least tau and the site with the greatest tau load (entorhinal cortex) had the least Abeta. The entorhinal and cingulate cortex are neuronally interconnected. Our results might be explained on the basis that a neurone with its cell body in the entorhinal cortex and axonal terminals in the cingulate cortex shows predominately tau pathology in relation to the cell body and predominately Abeta pathology in relation to its axonal terminals. We conclude that our observations are consistent with previously described models of AD progression. It is possible that tau-rich neurones are associated through their projections to Abeta rich sites. Further work of this kind analysing differential pathological profiles in interconnected brain regions may contribute to refining this model.

An automated method measures variability in P-glycoprotein and ABCG2 densities across brain regions and brain matter

“…The image analysis strategy developed here can also be used to identify other structures based on contrast with background. When a similar algorithm was used to measure plaque staining, it detected reported differences [19][20][21] in the post-mortem samples from both tissue sets. In set 1, plaque coverage was 60-87% higher in gray matter regions (versus white matter), in cortical regions (versus thalamus, a non-cortical region), and in AD patient samples (versus healthy) than in those of the respective controls.…”

A Longitudinal Study of Cognition, Proton MR Spectroscopy and Synaptic and Neuronal Pathology in Aging Wild-type and AβPPswe-PS1dE9 Mice

“…SIPBs were analyzed in the hippocampal regions stratum radiatum (SR) of the cornu ammonis (CA)1 area, stratum lucidum (SL) of the CA3 area, inner molecular layer (IML) and outer molecular layer (OML) of the dentate gyrus (DG), and in the cortical regions prelimbic area (PLA) and anterior cingulate gyrus (ACg). These regions were chosen because of their large amyloid load in AD patients and transgenic mouse models for AD and their importance in learning and memory [46], [47]. The ACg was quantified at level +1.10 up to +0.86 anterior to bregma using one appropriate section per animal, the PLA was quantified at +1.98 up to +1.78 anterior to bregma using one appropriate section per animal, and hippocampal regions were quantified at −2.18 up to −2.46 posterior to bregma using one appropriate section per animal.…”

Alternative neural circuitry that might be impaired in the development of Alzheimer disease

“…At the molecular level, a double dissociation in regional distribution of tau and amyloid-beta has been reported when comparing cingulate gyrus and enthorhinal cortex in post-mortem Alzheimer's brains (Shukla and Bridges, 1999 ). It was described that tau load was almost twice as great in the enthorinal cortex than elsewhere in the brain, whereas Aβ levels were much higher in the cingulate gyrus compared to enthorinal cortex (Shukla and Bridges, 1999 ).…”

“…At the molecular level, a double dissociation in regional distribution of tau and amyloid-beta has been reported when comparing cingulate gyrus and enthorhinal cortex in post-mortem Alzheimer's brains (Shukla and Bridges, 1999 ). It was described that tau load was almost twice as great in the enthorinal cortex than elsewhere in the brain, whereas Aβ levels were much higher in the cingulate gyrus compared to enthorinal cortex (Shukla and Bridges, 1999 ). It should be known if those differences may play a role in the development of the disease, mainly within the cingulate cortex, although we know that EC and posterior cingulate cortex could be interconnected and that modified tau could spread from EC to the cingulate cortex (Yassa, 2014 ).…”