The spatial patterns of ?/A4 deposit subtypes in Alzheimer's disease

Abstract

The spatial patterns of diffuse, primitive, classic (cored) and compact (burnt-out) subtypes of beta/A4 deposits were studied in coronal sections of the frontal lobe and hippocampus, including the adjacent gyri, in nine cases of Alzheimer's disease (AD). If the more mature deposits were derived from the diffuse deposits then there should be a close association between their spatial patterns in a brain region. In the majority of tissues examined, all deposit subtypes occurred in clusters which varied in dimension from 200 to 6400 microns. In many tissues, the clusters appeared to be regularly spaced parallel to the pia or alveus. The mean dimension of the primitive deposit clusters was greater than those of the diffuse, classic and compact types. In about 60% of cortical tissues examined, the clusters of primitive and diffuse deposits were not in phase, i.e. they alternated along the cortical strip. Clusters of classic deposits appeared to be distributed independently of the diffuse deposit clusters. Cluster size of the primitive deposits was positively correlated with the density of the primitive deposits in a tissue but no such relationship could be detected for the diffuse deposits. This study suggested that there was a complex relationship between the clusters of the different subtypes of beta/A4 deposits. If the diffuse deposits do give rise to the primitive and classic varieties then factors unrelated to the initial deposition of beta/A4 in the form of diffuse plaques were important in the formation of the mature deposits.

A critical analysis of the ‘amyloid cascade hypothesis’

“…Studies also suggest that SP and NFT exhibit distinct but independently distributed topographic patterns in the cerebral cortex in AD [12,64]. Braak and Braak [22] showed that tau pathology occurred first in entorhinal cortex, often in the absence of SP, whereas the subsequent spread and distribution of Aβ was more variable.…”

“…Perez et al [103], however, showed that Aβ [25][26][27][28][29][30][31][32][33][34][35] could result in tau aggregation and that a decrease in Aβ aggregation was induced by tau peptides. Hence, aggregation of tau may be correlated with disassembly of Aβ which could explain the lack of spatial correlation [12]. In addition, SP and NFT may be temporally separated in the brain [82].…”

The microglial phagocytic role with specific plaque types in the Alzheimer disease brain

“…Many studies fail to support the hypothesis that diffuse plaques evolve into dense-core plaques over time [2,38,60,65,72] suggesting that all plaques are not created equally, and that distinctive plaque types do not exchange in the brain [11,12,14,46,72]. For example, the majority of the A␤ deposits in the APP22 mice are the diffuse type, while those detected in the APP23 mice develop almost exclusively the dense-core, congophilic at their first appearance making it very difficult to reconcile the diffuse plaque types form a precursor for the dense-core congophilic plaques [60].…”

Can neurodegenerative disease be defined by four ‘primary determinants’: anatomy, cells, molecules, and morphology?

“…The pathology may then spread among cortical gyri and to subcortical regions via cortico-cortical and cortical-subcortical pathways respectively [5,45,136]. This hypothesis is supported by studies of the spatial patterns of SP and NFT [6,13] and of transgenic mice, in which there is selective disruption of cortico-cortical pathways [47]. Furthermore, this pattern of neurodegeneration correlates with specific neurotransmitter deficits, e.g., acetylcholinesterase-immunoreactive neurites are present at the periphery of SP, which could represent the degeneration of ascending and cortical cholinergic pathways [157].…”