The Ratio of Diffuse to Mature Beta/ A4 Deposits in Alzheimer's Disease Varies in Cases with and without Pronounced Congophilic Angiopathy

Abstract

The density of diffuse, primitive, classic and compact Β/A4 deposits was estimated in the cortex and hippocampus in Alzheimer's disease (AD) cases with and without pronounced congophilic angiopathy (CA). The total density of Β/A4 deposits in a given brain region was similar in cases with and without CA. Significantly fewer diffuse deposits and more primitive/classic deposits were found in the cases with CA. The densities of the primitive, classic and compact deposits were positively correlated in the cases without CA. However, no correlations were observed between the density of the mature subtypes and the diffuse deposits in these cases. In the cases with CA, the density of the primitive deposits was positively correlated with the diffuse but not with the classic deposits. The data suggest that the mature Β/A4 deposits are derived from the diffuse deposits and that the presence of pronounced CA enhances their formation.

Quantitative Differences in β/A4 Protein Subtypes in the Parahippocampal Gyrus and Frontal Cortex in Alzheimer's Disease

“…Current evidence suggests that the primitive and classic deposits develop from the diffuse deposits [12,24], If this assumption is correct, then the formation of mature deposits appears to be enhanced or accelerated in the PHG compared with the frontal cortex in our cases. However, increased density of mature deposits in sulci appears to reflect greater (3/A4 deposition rather than enhanced conversion.…”

“…The formation of amyloid may depend on pH and the local ionic environment [20,21], the presence of the C-terminus region of the amyloid pre cursor protein [22] and 'amyloid-enhancing factors' [23]. It is also possible that different factors are involved in the formation of primitive and classic deposits [24], Blood proteins have been recorded in amyloid cores [25][26][27] and it is possible that the formation of the classic deposits could depend on factors which diffuse from blood vessels [24], Although a greater number of all types of |3/A4 deposit was recorded in the depths of the sulci [14], their ratio to total [3/A4 density was relatively constant in sulci and gyri. Hence, the increased density of mature deposits in sulci is likely to be due to increased |3/A4 deposition.…”

Beta-Amyloid Deposition in the Temporal Lobe of Patients with Dementia with Lewy Bodies: Comparison with Non-Demented Cases and Alzheimer’s Disease

“…First, the density of the classic deposits was significantly lower in DLB/AD cases. In AD, the proportion of classic deposits is often increased in cases which have a significant degree of congophilic amyloid angiopathy [26]. Hence, the reduction in classic deposits in the DLB/AD patient group could reflect the reduced frequency of congophilic amyloid angiopathy that has been reported in DLB [27].…”

Beta-Amyloid Deposition in the Medial Temporal Lobe in Elderly Non-Demented Brains and in Alzheimer’s Disease

“…Second, p/A4 deposition may occur in a variety of dementias other than AD including Parkinson's disease and Creutzfeldt-Jacob disease [8,11], Third, the production of APP and the appearance of p/A4 could be a response to neuronal injury and the loss of synaptic con nections in the brain [12,13], If the deposition of ß/A4 is important in AD, then significant differences should be present in non-demented and AD brains e.g. in the densi ty and distribution of ß/A4 deposits [14], in the formation of mature versus diffuse ß/A4 deposits [15] or in the development of ß/A4 deposits in relation to the modular units of the cortex [3,16]. This study compared ß/A4 deposition in regions of the medial temporal lobe in elder ly non-demented brains and in AD to determine whether any of these differences could account for the develop ment of AD.…”