Interaction between Amyloid-β Pathology and Cortical Functional Columnar Organization

Abstract

Amyloid-␤ plaques are one of the major neuropathological features in Alzheimer's disease (AD). Plaques are found in the extracellular space of telencephalic structures, and have been shown to disrupt neuronal connectivity. Since the disruption of connectivity may underlie a number of the symptoms of AD, understanding the distribution of plaques in the neuropil in relation to the connectivity pattern of the neuronal network is crucial. We measured the distribution and clustering patterns of plaques in the vibrissae-receptive primary sensory cortex (barrel cortex), in which the cortical columnar structure is anatomically demarcated by boundaries in Layer IV. We found that the plaques are not distributed randomly with respect to the barrel structures in Layer IV; rather, they are more concentrated in the septal areas than in the barrels. This difference was not preserved in the supragranular extensions of the functional columns. When comparing the degree of clustering of plaques between primary sensory cortices, we found that the degree of plaques clustering is significantly higher in somatosensory cortex than in visual cortex, and these differences are preserved in Layers II/III. The degree of areal discontinuity is therefore correlated with the patterns of neuropathological deposits. The discontinuous anatomical structure of this area allows us to make predictions about the functional effects of plaques on specific patterns of computational disruption in the AD brain.

Abnormal Population Responses in the Somatosensory Cortex of Alzheimer’s Disease Model Mice

“…Beker et al . 72 showed that the Aβ plaques aggregates in the barrel cortex in a non-random pattern, the plaques are concentrated more in the septal areas than inside the barrels. Based on these findings, Beker and colleagues suggested that population responses in the barrel cortex of Tg mice will be much broader compared to Crtl mice.…”

Clustering of plaques contributes to plaque growth in a mouse model of Alzheimer’s disease

“…Accordingly, simulated plaques formed preferentially in the vicinity of existing plaques [32]. Additional support for the notion that plaques can cluster comes from another study showing that plaques in APP transgenic mice are non-randomly distributed and more concentrated in certain areas of the barrel cortex [3], which led the authors to suggest that neuronal architecture could determine where plaques deposit. A similar study discovered a correlation between neuronal activity and the spatial deposition of plaques [4].…”

“…Following initial plaque deposition, an immune response is triggered [24], which could be detrimental to the micro-environment [6] and increase the amount of plaque forming agents released from damaged neurons and glia. The micro-environment in which the initial plaque developed may be particularly favorable for additional plaque development [3, 4] so that multiple plaques preferentially develop within a very small area. Any or all of these factors could contribute to the non-random deposition of plaques in the vicinity of a pre-existing plaque.…”

Different trajectories of decline for global form and global motion processing in aging, mild cognitive impairment and Alzheimer's disease

“…Nevertheless, patients' performance of simple motionrelated tasks such as discriminating the direction of horizontal motion is typically more comparable to healthy controls' (Rizzo & Nawrot, 1998;Tetewsky & Duffy, 1999;Rizzo et al 2000;Mapstone et al, 2008). Many reports demonstrate much greater vulnerability to AD pathology in the long cortico-cortical projections of visual association cortex rather than in primary visual cortex (Lewis et al, 1987;Hof and Morrison, 1990;McKee et al, 2006;Beker et al, 2012;Carlyle et al, 2014), perhaps leading to more disrupted global than local processing (Beker et al, 2012). Taken together, these patterns suggest that lower level/local motion processing systems may be relatively preserved in AD, while higher level/global motion systems suffer more damage.…”

“…The patterns here indicate that although brain circuits involved in form recognition tasks are subject to age-and disease-related decline, performance is generally well preserved. Thus, in addition to a postulated greater vulnerability of global than local visual circuitry to AD pathology (Beker et al, 2012), global motion-related cortical systems may be more vulnerable than the equivalent form systems. This would fit with evidence that neurofibrillary tangles distinctively target very specific brain regions (e.g.…”