Tottori J. Clin. Res. 8(2), 202-209, 2017

Brief Communications

Brief literature review on the pathology of argyrophilic grain formation:
Based on an experience of a case of elderly dementia given a clinical diagnosis of Alzheimer’s disease, inwhom argyrophilic grains and neurofibrillary tangles were concomitantly observed at autopsy
Yoshihiro Konishi1)* Hirotake Nishimura2)
1) Department of Clinical Research, NHO Tottori Medical Center2) Department of Pathology I, Kawasaki Medical School*Correspondence: ykonishi@tottori-iryo.hosp.go.jp
We encountered an autopsy case involving a 93-year-old woman (at the time of death) in whom memory disturbance
had gradually progressed over an 11-year course. Both argyrophilic grains (AGs) and neurofibrillary tangles (NFTs)
were histopathologically observed, which may be generally reported as complications of argyrophilic grain dementia(AGD) or dementia with grains (DG) and senile dementia of the neurofibrillary tangle type (SD-NFT)1,2). We extensively
searched the literature on AGs in Japan and other countries; they indicated that AG lesions are additive and thepathology that we call AGs or AGD is a part of SD-NFT rather than a unique, distinct tauopathy causing dementia.
Tottori J. Clin. Res. 8(2), 202-209, 2017
Key Words: argyrophilic grains (AGs), neurofibrillary tangles (NFTs), pretangles, Gallyas-Braak (GB) silver staining	 

Two hours after a natural death due to aging, anautopsy was conducted of the brain only. The brain
weighed 986 grams before fixation with formalinsolution. Macroscopically, gyral atrophy of the frontaland temporal cortices was observed. Coronal slices
showed that the amygdala, hippocampal head andbody, and parahippocampal gyrus were all extremelyatrophic (Fig. 1). The hippocampal trail was relativelypreserved.
Microscopically, neuronal loss, astrocytosis, andghost tangles were noted in this region over thehippocampal C1 subfield (Fig. 2). These changes weremore prominent in the anterior than in the posterior
hippocampus.
On Gallyas-Braak (GB) silver impregnation andimmunohistochemical
stainingwithantiphosphorylated tau antibody AT8 (Innogenetics),
pretangles, NFTs, and neuropil threads (NTs) weremainly observed in these atrophic regions (Fig. 3) andonly slightly in the temporal isocortex. Most of theisocortical areas lacked these abnormal findings. The
distribution of AT8-positive NFTs/NTs in the present
case corresponded to Braak NFT/NT stage III3,4).
On GB silver and AT8-immunohistochemical
stainings, AGs were present not only in the amygdala,ambient gyrus, hippocampus, and parahippocampal
gyrus but also in the insular cortex and the anterior
cingulate cortex (Figs. 3 and 4), corresponding to
Saito’s stage III5). On immunostaining with antibodies
specifically recognizing 3-repeat tau (3R-tau) (RD3,Merck Millipore) and 4-repeat tau (4R-tau)(TIP-4RT-P01, Cosmo Bio, Tokyo)6,7), AGs werepositive for 4R-tau, NFTs were positive for both 3Rand 4R-tau, and ghost tangles were positive for 3R-tau(Figs. 5 and 6). On immunohistochemistry with
anti-amyloid β-peptide (Aβ) antibody Aβ11–28 (IBL,Takasaki, Japan), positive plaques were observed
mainly in the isocortices, but not in the hippocampus
or the visual cortex (Fig. 7), corresponding to Thal’sAβ-phase 18). Most of the Aβ-positive deposits werediffuse plaques and not senile plaques with cores or
neuritic haloes.
On Western blot analysis of tau protein, a 60-, 64-,
and 68-kDa triplet pattern was detected in the
hippocampal formation, subiculum, near the sulcus
collateralis in the transentorhinal area, the base of thetemporal lobe, and the amygdaloid nucleus, showing
accumulations of 3R-tau (60 and 64 kDa) and 4R-tau(64 and 68 kDa) to similar levels in all regions. In themiddle temporal and anterior cingulate gyri, a 64- and