Staging of Argyrophilic Grains: An Age-Associated Tauopathy

Abstract

We have reported that the ambient gyrus is the site with the greatest accumulation of argyrophilic grains (AGs) and that the degeneration of the ambient gyrus is responsible for dementia with grains. Here we analyzed 1,405 serial autopsy cases from 2 hospitals and detected AGs only in cases older than 56 years of age. The distribution of AGs followed a stereotypic regional pattern. Thus, we propose the following staging paradigm: stage I: AGs restricted to the ambient gyrus and its vicinity; stage II: AGs more apparent in the anterior and posterior medial temporal lobe, including the temporal pole, as well as the subiculum and entorhinal cortex; and stage III: abundant AGs in the septum, insular cortex, and anterior cingulate gyrus, accompanying spongy degeneration of the ambient gyrus. Sixty-three of 65 (96.9%) argyrophilic grain stage III cases without other dementing pathology were classified as 0.5 or higher in the clinical dementia rating. Forty-seven of 50 dementia with grains cases (94%) were stage III and 3 were stage II. No association with apoE genotyping was detected. Our study further confirms that dementia with grains is an age-associated tauopathy with relatively uniform distribution and may independently contribute to cognitive decline in the elderly.

Clinical, neuropathological and genotypic variability in SNCA A53T familial Parkinson’s disease

“…5). The distribution of the pathology was consistent with AGD stage II according to Saito et al (2004) [36].…”

Argyrophilic grains: A distinct disease or an additive pathology?

“…[30] This latter study subsequently resulted in a proposed staging scheme for AG. [31] Both these authors have argued for the concept of argyrophilic grain disease independently contributing to dementia. Others have argued against this concept.…”

Evidence from spatial pattern analysis for the anatomical spread of α-synuclein pathology in Parkinson’s disease dementia

“…Parkinson's disease dementia (PDD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA) are characterized by the formation of cellular inclusions containing pathological forms of the pre-synaptic protein α-synuclein. These pathologies include Lewy bodies (LB), Lewy neurites (LN), and Lewy grains (LG) in PDD and DLB [33] and glial cytoplasmic inclusions (GCI) in MSA [31]. α-Synuclein is a small molecular weight protein which regulates the functioning of dopamine transporter and tyrosine hydroxylase [27].…”