Low amyloid (Aβ) plaque load and relative predominance of diffuse plaques distinguish argyrophilic grain disease from Alzheimer’s disease

Abstract

Argyrophilic grain disease constitutes one cause of late-onset dementia. Its classification among dementia disorders is still unclear because most of the reported argyrophilic grain disease cases are associated with neurofibrillary lesions (e.g. neurofibrillary tangles) which are also typical of Alzheimer's disease. In the present study we determine whether argyrophilic grain disease is associated with the senile plaques of Alzheimer's disease. The distribution and density of senile plaques was systematically investigated in 11 demented argyrophilic grain disease cases using Abeta immunohistochemistry and stereological techniques, and the results were compared with 11 Alzheimer's disease cases. All subjects with argyrophilic grain disease exhibited neurofibrillary changes corresponding to Braak stages I-III. Three of the 11 argyrophilic grain disease cases (27%) were completely devoid of Abeta deposits. In argyrophilic grain disease cases with senile plaques, the average total plaque-load was significantly lower (1%) than in Alzheimer's disease (3.1%) (P<0. 005). The regional distribution of the senile plaques and the proportion of diffuse vs. primitive or mature plaques in argyrophilic grain disease resembled values of senile plaques reported in non-demented elderly subjects, and was significantly different from Alzheimer's disease. Similarly the immunocytochemical profile of the Abeta deposition in argyrophilic grain disease resembled that of non-demented elderly subjects rather than that of subjects with Alzheimer's disease. As all argyrophilic grain disease cases under investigation were demented, including those devoid of senile plaques, the present study further supports the thesis that dementia in argyrophilic grain disease correlates more with the density and distribution of argyrophilic grains than with associated lesions of the Alzheimer-type.

Argyrophilic Grain Disease: Neuropathology, Frequency in a Dementia Brain Bank and Lack of Relationship with Apolipoprotein E

“…Given the advanced age of most individuals with AGD it is not surprising that many cases also had SP (19), which were most often characterized by diffuse amyloid deposits without significant neuritic change. It remains to be determined if this type of neuronal alteration inevitably leads to NFT.…”

Argyrophilic grain disease: A late‐onset dementia with distinctive features among tauopathies

“…Moreover, we have shown, that the regional distribution of SP and the proportion of diffuse versus primitive or mature plaques in AgD are similar to values of SP reported in non‐demented elderly, and is significantly different from AD. Similarly, the immunocytochemical profile of Aβ deposition in AgD resembles that of cognitively unimpaired elderly rather than that of AD 54 …”

“…Two large series of AgD cases, in total 238 cases, 11,54 revealed extension of neurofibrillary changes in the shape of NFT and NTh corresponding to early (entorhinal and limbic) Braak stages, which generally are not associated with a cognitive decline 55,56 …”

REVIEW: tau protein pathology in Alzheimer’s disease and related disorders

“…ArGs are often associated with NFL and SP of AD and it has therefore been questioned whether AgD constitutes a nosological entity distinct from AD. However, comparing large numbers of AD and AgD cases, we have found a number of divergent features between the two disorders: (i) the cognitive status of patients with AgD is related to the extent of ArGs in limbic structures and not to associated changes of the AD‐type [ 104, 108]; (ii) the overall Aβ (plaque) load is significantly lower, and the relative amount of diffuse Aβ deposits is higher in AgD than in AD [ 104]; (iii) the apolipoprotein E ε4 allele frequency is significantly lower in AgD compared to AD but not to age‐matched control cases [ 33, 107]; and (iv) divergent morphological features also include the development of αB‐crystallin expressing ballooned neurones and the presence of peculiar tau‐immunoreactive non‐argyrophilic astrocytes (Figure 3 f ) in the amygdala of AgD but not AD cases [ 7, 106]. The latter clearly differ from tufted astrocytes of PSP, astrocytic plaques of CBD and non‐specific thorn‐shaped astrocytes which all contain argyrophilic glial fibrillary tangles (Figure 2 d , f ; Figure 3 d , e ; see below) [ 7, 16, 59, 61].…”