Differences in β-amyloid ( β A4) deposition in human patients with Down's syndrome and sporadic Alzheimer's disease

The density of diffuse, primitive, classic and compact β-amyloid ( β A4) deposits was estimated in the hippocampus and adjacent gyri in human patients with Down's syndrome (DS) and sporadic Alzheimer's disease (AD). The objective of the study was to determine whether there were differences in β A4 deposition in DS and sporadic AD and whether these differences could be attributed to overexpression of the amyloid precursor gene (APP) in DS. Total β A4 deposit density was greater in DS than AD in all brain regions studied but the DS/AD density ratios varied between brain regions. In the majority of brain regions, the ratio of primitive to diffuse β A4 deposits was greater in DS but the ratio of classic to diffuse deposits was greater in AD. The data were consistent with the hypothesis that overexpression of the APP gene in DS may lead to increased β A4 deposition. However, local brain factors also appear to be important in β A4 deposition in DS. Overexpression of the APP gene may also be responsible for increased production of paired helical filaments (PHF) and result in enhanced formation of primitive β A4 deposits in DS. In addition, increased formation of classic deposits in AD suggests that factors necessary for the production of a compact amyloid core are enhanced in AD compared with DS. © 1994.

Laminar distribution of amyloid-beta (Abeta) deposits in dementia with Lewy bodies: comparison with Alzheimer's disease

Significant amyloid-beta (Abeta) deposition in cases of dementia with Lewy bodies (DLB) may represent concurrent Alzheimer's disease (AD). To test this hypothesis, the laminar distribution of the diffuse, primitive, and classic Abeta deposits was studied in the frontal and temporal cortex in cases of DLB and were compared with AD. In DLB, the diffuse and primitive deposits exhibited two common patterns of distribution; either maximum density occurred in the upper cortical laminae or a bimodal distribution was present with density peaks in the upper and lower laminae. In addition, a bimodal distribution of the classic deposits was observed in approximately half of the cortical areas analysed. A number of differences in the laminar distributions of Abeta deposits were observed in DLB and AD. First, the proportion of the primitive relative to the diffuse and classic deposits present was lower in DLB compared with AD. Second, the primitive deposits were more frequently bimodally distributed in DLB. Third, the density of the diffuse deposits reached a maximum lower in the cortical profile in AD. These data suggest differences in the pattern of cortical degeneration in the two disorders and therefore, DLB cases with significant Abeta pathology may not represent the coexistence of DLB and AD.

Size frequency distribution of beta-amyloid (Abeta) deposits in dementia with Lewy bodies

In Alzheimer's disease (AD) and Down's syndrome (DS), the size frequency distribution of the beta-amyloid (Abeta) deposits can be described by a log-normal model and may indictae the growth of the deposits. This study determined the size frequency distribution of the Abeta deposits in the temporal lobe in 8 casaes of dementia with Lewy bodies (DLB) with associated AD pathology (DLB/AD. The size distributions of Abeta deposits were unimodal and positively skewed; the mean size of deposi and the degree of skew varying with deposit type and brain region. Size distributions of the primitive deposits had lower means and were less skewed compared with the diffuse and classic deposits. In addition, size distributions in the hippocampus and parahippocampal gyrus (PHG) had larger means and a greater degree of skew compared with other cortical gyri. All size distributions deviated significantly from a log-normal model. There were more Abeta deposits than expected in the smaller size classes and fewer than expected near the mean and in the larger size classes. The data suggest thatthe pattern of growth of the Abeta deposits in DLB/AD depends both on deposit morphology and brain area. In addition, Abeta deposits in DLB appear to grow to within a more restricted size range than predicted and hence, to have less potential for growth compared with cases of 'pure' AD and DS.

Lewy body and Alzheimer pathology in temporal lobe in dementia with Lewy bodies

The density of Lewy bodies (LB), senile plaques (SP), and neurofibrillary tangles (NFT) was studied in the temporal lobe in four patients diagnosed with ‘pure’ dementia with Lewy bodies (DLB) and eight patients diagnosed with DLB with associated Alzheimer’s disease (DLB/AD). In both patient groups, the density of LB was greatest in the lateral occipitotemporal gyrus (LOT) and least in areaas CA1 and CA4 of the hippocampus. In DLB/AD, the densities of SP and NFT were greatest in the cortical regions and in area CA1 of the hippocampus respectively. Mean LB densities in the temporal lobe were similar in ‘pure’ DLB and DLB/AD patients but mean SP and NFT densities were greater in DLB/AD. No significant correlations were observed between the densities of LB, SP and NFT in any brain region. The data suggest that in the temporal lobe LB and SP/NFT are distributed differently; SP and NFT in DLB/AD are distributed similarly to ‘pure’ AD and also that LB and AD pathologies appear to develop independently. Hence, the data support the hypothesis that some cases of DLB combine the features of DLB and AD.

Laminar distribution of cortical Lewy bodies and neurofibrillary tangles in dementia with Lewy bodies

The laminar distribution of Lewy bodies (LB) and neurofibrillary tangles (NFT) was studied in twelve cases of dementia with Lewy bodies (DLB). LB density was maximal in the lower cortex in 59% of cortical areas, in the upper cortex in 31% of areas while densities were similar in the upper and lower cortex in 9% of areas. The distribution of LB was either unimodal with a lower cortical peak, or bimodal with density peaks in the upper and lower cortex. The density of NFT was maximal in the upper cortex in all tissues. The distributions of LB and NFT were similar in temporal and frontal cortex and in cases with and without Alzheimer’s disease (AD). The vertical densities of LB and NFT were not significantly correlated. LB formation may affect the feedback cortico-cortical pathway and the efferent cortical projections whereas NFT formation may affect the feedforward cortico-cortical pathway.

A comparison of βamyloid (aβ deposition in the medial temporal lobe in late-onset sporadic Alzheimer's disease, and down's syndrome

The density of diffuse, primitive, classic and compact βamyloid (Aβ deposits was estimated in regions of the medial temporal lobe (MTL) in 15 cases of late-onset sporadic Alzheimer's disease (AD) and 12 cases of Down's syndrome (DS). A similar pattern of Aβ deposition was observed in the MTL in the AD and DS cases with a reduced density of deposits in the hippocampus compared with the adjacent cortical regions. Total Aβ deposit density was greater in DS than in AD in all brain regions examined. This could be attributable to overexpression of the amyloid precursor protein gene. The ratio of the primitive to the diffuse Aβ deposits was greater in DS than in AD which suggests that the formation of mature amyloid deposits is enhanced in DS. The diffuse deposits exhibited a parabolic and the primitive deposits an inverted parabolic response with age in the DS cases. This suggests either that the diffuse and primitive deposits are sequentially related or that there are alternate pathways of Aβ deposition. © 1995 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.

The spatial arrangement patterns of senile plaques in senile dementia of the Alzheimer type (SDAT)

The spatial arrangement patterns of senile plaques have been studied in 10 micron cresyl violet stained sections cut from embedded portions of 20 brain regions from SDAT brains. Two studies are reported: an initial study using the Poisson distribution and a subsequent study using pattern analysis. The initial study indicated that plaques are arranged in discrete clumps in all brain regions when examined at x100 and x400 – suggesting that both small and larger scale clumping may be present. The pattern analysis study was applied to 8 cortical regions. This technique allows a more detailed study of pattern to be made. In all regions the technique revealed that the basic pattern of plaque arrangement is the regularly spaced discrete clump – which may be present on both large and small scales.

A quantitative study of the neuropathology of 32 sporadic and familial cases of frontotemporal lobar degeneration with TDP-43 proteinopathy (FTLD-TDP)

To further characterize the neuropathology of the heterogeneous molecular disorder frontotemporal lobar degeneration (FTLD) with transactive response (TAR) DNA-binding protein of 43 kDa (TDP-43) proteinopathy (FTLD-TDP).

Dementia with Lewy bodies: a 'new' type of dementia with visual symptoms

Dementia with Lewy bodies (DLB) (also known as Lewy body dementia or diffuse Lewy body disease) is now recognised as the second most common type of dementia after Alzheimer's disease and may account for up to a quarter of all cases in elderly perople. This article decsribes the general symptoms of DLB and the visual symptoms that have been reported in the disorder.

Spatial arrangement patterns of senile plaques in post-mortem senile dementia of the Alzheimer type brains

We have studied the spatial distribution of plaques in coronal and tangential sections of the parahippocampal gyrus (PHG), the hippocampus, the frontal lobe and the temporal lobe of five SDAT patients. Sections were stained with cresyl violet and examined at two magnifications (x100 and x400). in all cases (and at both magnifications) statistical analysis using the Poisson distribution showed that the plaques were arranged in clumps (x100: V/M = 1.48 - 4.49; x400 V/M = 1.17 - 1.95). this indicates that both large scale and small scale clumping occurs. Application of the statistical techniques of pattern analysis to coronal sections of frontal and temporal cortex and PHG showed. furthermore, that both large (3200-6400 micron) and small scale (100 - 400 micron) clumps were arranged with a high degree of regularity in the tissue. This suggests that the clumps of plaques reflect underlying neural structure.

Size frequency distribution of senile plaques in post-mortem brains of five patients with senile dementia of the Alzheimer type (SDAT)

Numerous senile plaques are one of the most characteristic histological findings in SDAT brains. Large classical plaques may develop from smaller uncored forms. There is no strong evidence that, once formed, plaques disappear from the tissue. We have examined cresyl-violet stained sections of the parahippocampal gyrus (PHG), hippocampus, frontal lobe and temporal lobe of five SDAT patients. The frequency of various sizes of plaques were determined in each of these brain regions. Statistical analysis showed that the ratio of large plaques to small plaques was greater in the hippocampal formation (especially the PHG) than in the neocortex. One explanation of these results is that plaques grow more rapidly in the hippocampal formation than elsewhere. Alternatively, if the rate of plaque growth is much the same in different brain regions, the data suggest that plaques develop first in the hippocampal formation (especially the PHG) and only later spread to the neocortex. This interpretation is also consistent with the theory that the neuropathology of SDAT spreads from the olfactory cortex via the hippocampal formation to the neocortex. Further development of this technique may help identify the site of the primary lesion in SDAT.

Are there two distinct populations of cored senile plaques in senile dementia of the Alzheimer type?

The relationship between plaque diameter (PD) and core diameter (CD) was studied in four brains from each of four SDAT brains. The regions studied were parahippocampal gyrus (PHG), hippocampus, frontal and inferior temporal lobes. The largest diameters of 100 cored classical plaques and their cores were measured. CD was positively correlated with PD (Pearson's 'r' 0.4 - 0.95) in all region studied. Significant linear regressions of CD on PD with positive slopes (0.10 - 0.65) were found. Two distinct types of regression were found. Type A had a steep slope and a negative intercept on the ordinate whereas Type B had a shallow slope and a positive intercept. Both types can be found within the same brain but Type A or B predominate in a particular tissue. The data suggest that core development may occur either early or late in the development of the plaque. The two types of plaque may thus have different aetiologies. Such an interpretation is consistent with current ideas of plaque formation.

Tetrahydrobiopterin metabolism in senile dementia of the Alzheimer type (SDAT)

Tetrahydrobiopterin is the cofactor required for the biosynthesis of the neurotransmitters and neuromodulators dopamine, noradrenaline and serotonin. The results show that in SDAT there is decreased conversion of dihydroneopterin triphosphate to tetrahydrobiopterin. Further measurements on strictly age-matched SDAT subjects and controls have confirmed the trends in this investigation.

The case for aluminium as the neurotoxin in sporadic Alzheimer's disease

The flash-pattern evoked potential difference (F - P) in man increases with age (93 subjects), correlates with decreasing cognitive ability and when it exceeds a unique critical level the subject is clinically diagnosed as having Alzheimer's disease. Aluminium accumulates in the human brain with age, increases the F - P value close to the critical value in a dose dependent manner, and at such a rate that normal environmental exposure to aluminium accounts for all or nearly all the F - P increases in man. Aluminium neurotoxicity is therefore a major cause of sporadic Alzheimer's disease.

Relationships between beta-amyloid (Abeta) deposits and blood vessels in familial and sporadic Alzheimer's disease

Introduction: The density of diffuse, primitive and classic beta-amyloid (Abeta) deposits and blood vessels was studied in nine cases of sporadic Alzheimer's disease (SAD) and 10 cases of familial Alzheimer's disease (FAD) including two cases with amyloid precursor protein (APP) mutations (APP717, Val - Ile). Materials and Methods: Sections of frontal cortex stained for Abeta12-28 counterstained with collagen type IV antiserum. Densities measured along the upper cortex in 64-128, 1000 x 200 micron continuous sample fields. Results: The density of diffuse and primitive deposits was not correlated with blood vessels in FAD or SAD. The density of the classic deposits was positively correlated with the larger diameter (> 10 micron) blood vessels in all SAD cases and weakly correlated with blood vessel in three non-APP FAD cases. Conclusions: Blood vessels are less important in the formation of classic Abeta deposits in FAD compared with SAD.