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Neuropathology 2014; ••, ••–••

doi:10.1111/neup.12188

C a se Repor t

An autopsied case of corticobasal degeneration showing severe cerebral atrophy over a protracted disease course of 16 years Daizo Kondo,1,3 Hiroaki Hino,4 Katsuhiko Shibuya,4 Koshiro Fujisawa,4 Kenji Kosaka,3,4 Yoshio Hirayasu,3 Ryoko Yamamoto,1,2 Koji Kasanuki,1,2 Michiko Minegishi,1 Kiyoshi Sato,1 Masato Hosokawa,5 Tetsuaki Arai,5 Heii Arai2 and Eizo Iseki1,2 1

PET-CT Dementia Research Center, Juntendo Tokyo Koto Geriatric Medical Center, 2Department of Psychiatry, Juntendo University School of Medicine, Tokyo, 3Department of Psychiatry, Yokohama City University School of Medicine, 4Department of Psychiatry, Yokohama Hoyu Hospital, Yokohama and 5Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan

The patient was a 72-year-old Japanese woman. At the age of 57, she started having difficulty performing daily work and developed agraphia. She also exhibited restlessness and loss of interest, and began to speak less. Thereafter, stereotypical behavior, gait disturbance and dysphagia were noted. CT scan demonstrated leftdominant frontal and temporal lobe atrophy. She died at the age of 72, about 16 years after the onset of symptoms. Neuropathologically, the brain weighed 867 g, and showed remarkable cerebral atrophy with degeneration of the white matter, predominantly in the left dorsal frontal lobe and anterior temporal lobe. Microscopically, severe neuronal loss and gliosis with rarefaction were found in the cerebral cortex, and severe destruction of myelin and axons was observed in the cerebral white matter. Moderate neuronal loss with gliosis was also found in the pallidum and substantia nigra. Gallyas-Braak staining and tau immunostaining revealed pretangle neurons, NFTs, ballooned neurons and astrocytic plaques in the cerebral cortex, subcortical nuclei and brainstem, and argyrophilic threads and coiled bodies in the subcortical white matter. Tau isoform-specific immunostaining revealed that most tau-immunoreactive structures were positive for 4-repeat (4R) tau, but some of the NFTs were positive for 3-repeat (3R) tau in the cerebral neocortex. Immunoblotting

Correspondence: Eizo Iseki, MD, PhD, PET/CT Dementia Research Center, Juntendo Tokyo Koto Geriatric Medical Center, Juntendo University School of Medicine, 3-3-20 Shinsuna, Koto-ku, Tokyo 1360075, Japan. Email: [email protected] Received 9 September 2014; revised 5 November 2014 and accepted 6 November 2014.

© 2014 Japanese Society of Neuropathology

demonstrated an accumulation of 4R tau in the cerebral cortex and subcortical white matter. The patient was pathologically diagnosed as having corticobasal degeneration. Her long survival course likely accounts for the severe white matter degeneration and accumulation of 3R tau in NFTs. Key words: abnormal tau structure, corticobasal degeneration, long-survival course, severe white matter degeneration, tau isoform.

INTRODUCTION Corticobasal degeneration (CBD) was first reported as a clinicopathologically distinct neurodegenerative disease by Rebeiz et al.1 in 1968, and its clinicopathological and biochemical features have been described from 1985 onwards.2,3 However, CBD exhibits various clinical features, and some neurodegenerative diseases other than CBD have been reported to manifest clinical features similar to those of CBD.3–6 Therefore, CBD is now used as a pathological diagnostic term for a set of common pathological features, while corticobasal syndrome is used for clinical diagnosis3 and is frequently included in frontotemporal degeneration.7,8 CBD is clinically characterized by asymmetry of symptoms, apraxia, cortical sensory disturbance, cerebral cortical signs, such as alien hand syndrome, and extrapyramidal signs such as levodopa-resistant muscle rigidity, akinesia, dystonia and myoclonus. CBD generally develops between the ages of 50 and 60, and its clinical course is approximately 6–8 years.9 CBD is pathologically characterized by neuronal loss and gliosis in the cerebral cortex and various subcortical nuclei, but degeneration of the cerebral white

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Fig. 1 CT scan findings taken about 14 years after onset. The brain shows bilateral severe cortical and subcortical atrophy with dilatation of the lateral ventricles.

matter is also observed. In addition, CBD is biochemically a tauopathy, and an abnormal accumulation of tau is found in both neurons and glia. The detection of abnormal tau structures in neurons and glia is useful for the pathological diagnosis of CBD, which includes the presence of pretangle neurons, NFTs, ballooned neurons and astrocytic plaques in the cerebral cortex and subcortical nuclei, and the occurrence of argyrophilic threads and coiled bodies in the subcortical white matter.10–12 These abnormal tau structures are composed of an accumulation of 4-repeat (4R) tau, a tau isoform, and CBD is now classified as a 4R tauopathy, along with PSP and argyrophilic grain disease (AGD).10,13 In this study, we report an autopsied case of CBD showing severe cerebral atrophy, with a protracted disease course of 16 years, for which CBD was pathologically and biochemically investigated. This case displayed various abnormal tau structures typical of CBD in the brain, although they were fewer in number compared with shortsurvival CBD cases, especially in the cerebral white matter. In addition, most of the abnormal tau structures were immunohistochemically composed of an accumulation of 4R tau, which was confirmed by immunoblotting, but some NFTs were composed of 3-repeat (3R) tau in the cerebral neocortex, despite the absence of concomitant Alzheimer’s disease (AD).

CLINICAL SUMMARY The patient was a 72-year-old Japanese woman. She had neither a past history nor a family history of neurological disease. At the age of 57, she started to have difficulty performing her daily work and developed agraphia. Although she could drive and work, she gradually exhibited restlessness, loss of interest and began to speak less. At the age of 61, she was diagnosed as having AD. Thereafter, stereotypical behavior, gait disturbance and dysphagia were noted. At the age of 67, when she was admitted

to the hospital, she was in an almost apallic state without spontaneity. Moreover, limb myoclonus was frequently induced by stimulation, and she became bedridden with contracture of the extremities, and required tube feeding because of pseudobulbar palsy. CT scan demonstrated severe cerebral atrophy, predominantly in the left frontal and temporal lobes, and finally revealed bilateral severe cortical and subcortical atrophy with dilatation of the lateral ventricles (Fig. 1A–C). Based on these findings, she was diagnosed as having CBD. After admission, she experienced repeated aspiration pneumonia and urinary tract infection and died of ileus at the age of 72, 16 years after her initial symptoms.

NEUROPATHOLOGICAL FINDINGS Macroscopic findings The brain weighed 867 g, and was fixed in 4% paraformaldehyde in 0.1 mol/L phosphate buffer, pH 7.4. The cerebrum showed remarkable atrophy in the dorsal frontal and anterior temporal lobes, and in the precentral and postcentral gyri, predominantly on the left side (Fig. 2A). The posterior parieto-temporal and occipital lobes were relatively preserved. Brain slices demonstrated narrowing of the cerebral cortex and atrophy of the cerebral white matter, and the deep white matter was soft (Fig. 2B). The hippocampus and amygdala were also atrophic, and dilatation of the inferior horns of the lateral ventricles was observed. The subcortical nuclei, including the caudate nucleus, putamen, pallidum and thalamus, showed atrophy, and the pallidum and lateral dorsal nucleus of the thalamus were brown in color (Fig. 2C). The tegmentum of the brain stem showed atrophy, predominantly in the midbrain and pons. The substantia nigra and locus ceruleus demonstrated decreased pigmentation (Fig. 2D). The cerebellum was not remarkable. © 2014 Japanese Society of Neuropathology

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Fig. 2 (A) The cerebrum shows remarkable atrophy in the dorsal frontal, anterior temporal lobes, precental and postcental gyri. (B) The cerebral slices demonstrate narrowing of the cerebral cortex and atrophy of the cerebral white matter. (C) The hippocampus and amygdala are atrophic with dilatation of the inferior horns of lateral ventricles. The caudate nucleus, putamen and pallidum show atrophy, and the pallidum is brown in color. (D) The substantia nigra demonstrates decreased pigmentation.

Light microscopic findings Brain slices were embedded in paraffin, cut into 6-μm-thick sections, and stained with HE, KB and Gallyas-Braak (GB) methods for pathological examination. The cerebral cortex showed mild to severe neuronal loss with gliosis, especially in the superior frontal and precentral cortices, accompanied by status spongiosis in the superficial layers (Fig. 3A). In addition, some ballooned neurons (Fig. 3B), many GB-positive NFTs (Fig. 3C), pretangle neurons (Fig. 3D) and some GB-positive astrocytic plaques (Fig. 3E) were visible in the deep layers. The hippocampus also showed severe neuronal loss with gliosis. In the subcortical nuclei, mild to moderate neuronal loss with gliosis and a few ballooned neurons were observed, especially in the caudate nucleus and putamen. The cerebral white matter showed severe degeneration with gliosis, destruction of myelin and axons (Fig. 3F), especially in the deep white matter, and many GB-positive argyrophilic threads and coiled bodies (Fig. 3G), especially in the subcortical white matter. In the brain stem and cerebellum, mild to moderate neuronal loss with gliosis was observed in the tegmentum of the midbrain and pons, and © 2014 Japanese Society of Neuropathology

in the substantia nigra (Fig. 3H). The pyramidal tract, including the cerebral peduncle and pyramis, showed mild myelin pallor. The degree of neuronal loss with gliosis and the number of ballooned neurons were semiquantitatively evaluated for some brain regions using HE staining (field size: 0.66 mm2). Neuronal loss with gliosis was graded as follows: −, absent; 1, slight; +, mild; ++, moderate, severe. The number of ballooned neurons was graded as follows: −, absent; 1, rare; +, small number; ++, moderate number, large number. The results are presented in Table 1.

Immunohistochemical findings The paraffin-embedded sections were immunostained using the following primary antibodies: anti-phosphorylated tau (AT8, monoclonal, mouse, 1:2000; Innogenetics, Ghent, Belgium), anti-α-synuclein (PSer129, monoclonal, mouse, 1:20 000; donated by Dr T. Iwatsubo)14 and anti-Aβ (polyclonal, rabbit, 1:2000; donated by Dr H. Akiyama). In addition, anti-3R tau-specific and anti-4R tau-specific (RD3 and RD4, respectively, monoclonal, mouse, 1:100; donated by Dr Rohan de Silva) antibodies

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Fig. 3 (A) Severe neuronal loss with gliosis and status spongiosis in the superior frontal cortex. (B) A ballooned neuron in the precentral cortex. (C) An NFT in the precentral cortex. (D) A pretangle in the precentral cortex. (E) An astrocytic plaque in the precentral cortex. (F) Severe degeneration with destruction of myelins in the cerebral white matter. (G) Some argyrophilic threads and coiled bodies in the cerebral white matter. (H) Moderate neuronal loss with gliosis and in the substantia nigra. (A,B,H) HE staining. (C–E,G) Gallyas-Braak staining. (F) KB staining. Bars A,E–H 60 μm; B–D 30 μm.

© 2014 Japanese Society of Neuropathology

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Table 1 Regional degrees of neuronal loss with gliosis, ballooned neurons and AT-8 positive structures

Cerebral cortex Superior frontal Inferior frontal Precentral Postcental Middle temporal Occipital Entorhinal Hippocampus Subcortical area Amygdala Meynert nucleus Caudate&putamen Globus pallidus Thalamus Subcortical white matter Deep white matter Brainstem Midbrain tegmentum Red nucleus Substantia nigra Locus ceruleus Pontine tegmentum Pontine nucleus Inferior olivary nucleus Cerebellum Dentate nucleus Cerebellar white matter

Neuronal loss with gliosis

BN

NFT

PT

AP

CB

AT

+++ + +++ ++ 1 + ++ +++

+ + ++ + 1 + 1 −

+++ ++ +++ ++ + + +++ +++

+++ ++ +++ + + + +++ +++

+++ +++ +++ ++ + + − −

++ + ++ + + + + +

+++ ++ +++ ++ + + +++ +++

+ + ++ + 1

+ − + − −

+++ ++ ++ ++ +

+++ ++ ++ ++ ++

− − − − −

+ + + ++ ++ +++ +

+ + ++ +++ +++ ++ +

++ 1 ++ + ++ 1 +

− − − − − − −

++ + +++ +++ ++ ++ ++

++ ++ +++ +++ ++ ++ ++

− − − − − − −

++ ++ ++ ++ ++ + +++

++ ++ ++ ++ ++ + +++

+



++

++



++ +

++ +

AP, astrocytic plaques; AT, argyrophilic threads; BN, ballooned neurons; CB, coiled bodies; NFT, neurofibrillary tangles; PT, pretangles.

were also used in this study. These antibodies have been characterized and their specificities have been confirmed in previous reports.15,16 Immunolabeling was detected using the ABC method (Elite Kit, Vector, Burlingame, CA,USA) and visualized with diaminobenzidine (DAB; Wako, Osaka, Japan). Anti-Aβ and anti-α-synuclein antibodies were applied after pretreating the sections with 70% formic acid for 10 min, and RD3 and RD4 antibodies were applied after treating the sections with 70% formic acid for 10 min and hydrated autoclaving at 120°C for 10 min. For RD3 immunostaining, additional pretreatment with potassium permanganate followed by oxalic acid was performed to eliminate normal 3R tau in neurons.17 The cerebral cortex showed many AT8-positive NFTs and pretangle neurons (Fig. 4A), with some AT8-positive astrocytic plaques (Fig. 4B), especially in the superior frontal, precentral and entorhinal cortices and hippocampus. In the subcortical nuclei, many AT8positive NFTs and pretangle neurons were found, especially in the amygdala, Meynert nucleus, caudate nucleus, putamen and pallidum. In the cerebral white matter, many AT8-positive coiled bodies (Fig. 4C) and numerous AT8-positive argyrophilic threads were found, especially © 2014 Japanese Society of Neuropathology

in the subcortical white matter. In the brain stem and cerebellum, many AT8-positive NFTs and pretangle neurons were found, especially in the substantia nigra and locus ceruleus. Aβ-positive senile plaques, amyloid deposits and α-synuclein-positive Lewy bodies were not found in any region of the brain. All pretangle neurons (Fig. 4D), astrocytic plaques, threads, coiled bodies (Fig. 4E) and argyrophilic threads were RD4-positive. Most NFTs were RD4-positive, while some flame-shaped RD3-positive NFTs were observed in the hippocampus and entorhinal cortex (Fig. 4F), juxtaposed with some flame-shaped RD4-positive NFTs. In addition, some globe-shaped RD3-positive NFTs in the cerebral neocortex were mixed with many globe-shaped RD4-positive NFTs (Fig. 4G). RD3 immunostaining of sections pretreated with potassium permanganate followed by oxalic acid showed similar results (Fig. 4H,I). AT8-positive structures were semiquantitatively evaluated for some brain regions (field size: 0.66 mm2). AT8positive NFTs and pretangle neurons were graded as follows: −, absent; +, one or two per ×200 field; ++, three to five per ×200 field, more than six per ×200 field. AT8positive astrocytic plaques were graded as follows:

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Fig. 4 (A) An NFT (arrow) and a pretangle (arrow head) in the precentral cortex. (B) An astrocytic plaque in the precentral cortex. (C) A coiled body in the cerebral white matter. (D) A RD4-positive pretangle in the precentral cortex. (E) A RD4-positive coiled body in the cerebral white matter. (F) A RD3-positive NFT (flame-shaped type) in the entorhinal cortex. (G) A RD3-positive NFT (globose-shaped type) in the precentral corex. (H) A RD3-positive NFT (flame-shaped type) in the entorhinal cortex. (I) A RD3-positive NFT (globoseshaped type) in the precentral corex. (A–C) AT8-immunostaining. (D,E) RD4-immunostaining. (F,G) RD3-immunostaining. (H,I) RD3immunostaining after pretreatment with potassium permanganate and oxalic acid. Bars B 60 μm; A,C–I 30 μm.

−, absent; +, one per ×100 field; ++, two or three per ×100 field, more than four per ×100 field. AT8-positive coiled bodies were graded as follows: −, absent; +, one to three per ×200 field; ++, four to nine per ×200 field, more than 10 per ×200 field. AT8-positive argyrophilic threads were graded as follows: 0, absent; +, some; ++, many, numerous. The results are presented in Table 1.

NEUROCHEMICAL FINDINGS Immunoblotting of insoluble tau Sarcosyl-insoluble tau was extracted from the frontal lobe. Following electrophoresis, proteins were electrotransferred onto a polyvinylidene fluoride membrane (Millipore,

USA). After blocking with 3% gelatin in TRIS-buffered saline (20 mmol/L TRIS, pH 7.6, 500 mmol/L NaCl), the membranes were incubated overnight with primary antibody. Following incubation with an appropriate biotinylated secondary antibody, immunolabeling was detected using the ABC system (Vector) with 5-bromo-4chloro-3-indolylphosphate p-toluidine salt (BCIP) and nitroblue tetrazolium chloride (NBT) as chromogens.Antibodies used in this study were HT7 and PHF-1 (Zymed, San Francisco, CA, USA), which recognize the C-terminal region of tau. On immunoblots of sarcosyl-insoluble tau stained with HT7 (Fig. 5A) or PHF-1 (Fig. 5B), dephosphorylated insoluble tau appeared as 4R tau isoforms in both the cerebral gray matter and white matter. The low-molecular-weight © 2014 Japanese Society of Neuropathology

Long-survival course of CBD

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AnƟbody: HT7(1:3000) (A)

Rec

CBDG

CBDW

- +

- +

AnƟbody: PHF(1:1000) (B)

37kDa

Fig. 5 Immunoblots of sarcosyl-insoluble tau. (A,B) Immnoblots of sarcosyl-insoluble tau from the frontal lobe stained with HT7 (A) and PHF (B). (A) Tau isoforms of insoluble tau are 4R-tau both in the cerebral gray matter (CBDG) and white matter (CBDW). (B) C-terminal regions of insoluble tau are predominantly 37 kDa both in CBDG and CBDW. The banded color of tau was lighter in CBDW than in CBDG. (CBD: corticobasal degeneration, AD: Alzheimer’s disease).

Table 2 Clinicopathological data of CBD patients with a long-survival course Author

Mizuno et al. (2002)18 Wakabayashi et al. (2006)19 Zhang et al. (2009)20 Homma et al. (2013)21 This case

Age (years)

Disease course (years)

Brain weight (g)

63 63 72 66 56

12 12 10 9 16

820 785 1040 940 867

fragments clearly contained a 37-kDa band in both the cerebral gray matter and white matter. In an analysis of insoluble tau, the banded color of tau was lighter in the cerebral white matter than in the cerebral gray matter.

DISCUSSION In this study, the patient initially developed agraphia and cerebral cortical signs such as aphasia and apraxia, followed by extrapyramidal signs such as gait disturbance, dysphagia and myoclonus, and finally fell into an apallic state. CT scan initially showed left-dominant atrophy of the frontal and temporal lobes, and finally bilateral severe cerebral atrophy. These clinical features are consistent with those of CBD. The pathological features of this case included: (i) neuronal loss with gliosis in the cerebral cortex, subcortical nuclei and brain stem; (ii) the presence of ballooned neurons in the cerebral cortex and subcortical © 2014 Japanese Society of Neuropathology

Clinical features (initial symptom) Amnesia Aphasia Aphasia Apraxia Agraphia

Degeneration of cerebral white matter

Nonspecific pathological features

Severe Severe Severe Moderate Severe

Iron deposition Aβ deposition Aβ deposition Aβ deposition 3R-tau accumulation in NFT

nuclei; and (iii) the extensive occurrence of abnormal tau structures in neurons (NFTs, pretangle neurons and threads) and glia (astrocytic plaques, coiled bodies and argyrophilic threads). In addition, most of these abnormal tau structures were immunohistochemically and biochemically composed of an accumulation of 4R tau. These pathological features are also consistent with those of CBD. However, while the clinical course of CBD is generally 6–8 years, that of this case persisted for 16 years, which is the longest clinical course among reported CBD cases. The clinicopathological characteristics of this case are compared with those of previously reported long-survival CBD cases in Table 2. CBD manifests various clinical features, which are not disease-specific in the early stage in many CBD cases.22 When the clinical features of CBD are roughly divided into cerebral cortical and extrapyramidal signs, cerebral cortical signs such as amnesia, aphasia and apraxia precede

8 extrapyramidal signs in long-survival CBD cases.18–21 Pathologically, in addition to CBD-specific pathological features, nonspecific pathological features, including concomitant AD pathology such as amyloid deposition, are frequently observed in long-survival CBD cases.18–21 Severe neuronal loss associated with these specific and nonspecific pathological features mainly involves the cerebral cortex, and may be preceded by cerebral cortical signs. The extensive neuronal loss results in severe cortical degeneration, as displayed by this case. This case exhibited several pathological features likely influenced by the long-survival course. One of the pathological features characteristic of this case is severe white matter degeneration. Although white matter degeneration is also observed in short-survival CBD cases, it is not as severe.23 In long-survival CBD cases, the cerebral white matter is severely degenerated, in addition to severe cortical degeneration (Table 2). Relevant to the observed white matter degeneration, Tan et al.24 demonstrated specific metabolic changes in long-survival CBD, which might result in the accumulation of abnormally phosphorylated tau in oligodendroglia (coiled bodies and argyrophilic threads) and cause cell death. Ohara et al.25 reported that many tau-positive fibrils accumulated in the subcortical white matter in an atypical CBD case, resulting in white matter degeneration. In their patient, white matter degeneration was more severe in the deep white matter than in the subcortical white matter, while the number of abnormal tau structures was greater in the subcortical white matter than in the deep white matter. This suggests that abnormal tau accumulation may result in severe loss of oligodendroglia over the protracted disease course in longsurvival patients. This oligodendroglial loss likely leads to severe white matter degeneration in the deep white matter, preceded by subcortical white matter degeneration. Another pathological feature characteristic of this case is the mixed accumulation of 4R tau with 3R tau in abnormal tau structures. Abnormal tau structures in CBD are composed of an accumulation of 4R tau, a tau isoform, and CBD is considered a 4R tauopathy, along with PSP and AGD.10,13,16,26 CBD and PSP have similar pathological and biochemical features. However, in the low-molecularweight tau protein fraction on immunoblots of sarcosylinsoluble brain extract, the 33-kDa band is the main component in PSP, whereas two bands are present at 37-kDa in CBD,27 suggesting a biochemical difference between the two diseases. In the present case, an accumulation of 4R tau in the brain was confirmed by immunoblotting, and the 37-kDa band was the dominant C-terminal pattern of insoluble tau; therefore this case is biochemically consistent with CBD. However, most of the abnormal tau structures were immunohistochemically positive for 4R tau, while some NFTs in the cerebral cortex

D Kondo et al. were positive for 3R tau. This observation of 3R taupositive NFTs was confirmed by pretreatment with potassium permanganate followed by oxalic acid.17 Some of the 3R tau-positive NFTs in the hippocampus and entorhinal cortex were flame-shaped, suggesting that they may develop with age in this case, similar to nondemented elderly subjects. In comparison, some NFTs in the cerebral neocortex were globose-shaped type, suggesting that they may be typical of CBD, because this case had no concomitant AD (in which 3R + 4R tau-positive NFTs are present).26 We previously reported an immunohistochemical study on the characteristics of NFTs and tau isoforms in patients with limbic NFT dementia (LNTD), represented by NFTonly dementia.28 In LNTD, many NFTs are observed in the limbic area without amyloid deposition. We showed that NFT formation progresses from pretangle neurons to NFT, and finally, to ghost tangles (GTs). In addition, we found that the main tau isoforms in pretangle neurons, NFTs and GTs are 4R tau, 4R + 3R tau and 3R tau, respectively, suggesting that the major tau component may switch from 4R to 3R as NFT formation progresses. In our present long-survival case, the presence of 3R tau-positive NFTs in the cerebral neocortex suggests that the principal tau component in NFTs may switch from 4R tau to 3R tau over the extended disease course. In conclusion, this case was clinicopathologically and biochemically diagnosed as having CBD. The long-survival course of this case may account for the severe white matter degeneration and the presence of NFTs with 3R tau accumulation.

ACKNOWLEDGMENTS We are grateful to Dr T. Iwatsubo, Dr H. Akiyama and Dr Rohan de Siliva for the generous supply of antibodies. The authors have declared no conflicts of interest.

REFERENCES 1. Rebeiz JJ, Kolodny EH, Richardson EP Jr. Corticodentatonigral degeneration with neuronal achromasia. Arch Neurol 1968; 18: 20–33. 2. Gibb WR, Luthert PJ, Marsden CD. Corticobasal degeneration. Brain 1989; 112: 1171–1192. 3. Boeve BF, Lang AE, Litvan I. Corticobasal degeneration and its relationship to progressive supranuclear palsy and frontotemporal dementia. Ann Neurol 2003; 54: S15–S19. 4. Ling H, O’Sullivan SS, Holton JL et al. Does corticobasal degeneration exist? A clinicopathological re-evaluation. Brain 2010; 133: 2045–2057. © 2014 Japanese Society of Neuropathology

Long-survival course of CBD 5. Lee SE, Rabinovici GD, Mayo MC et al. Clinicopathological correlations in corticobasal degeneration. Ann Neurol 2011; 70: 327–340. 6. Boeve BF. The multiple phenotypes of corticobasal syndrome and corticobasal degeneration: implications for further study. J Mol Neurosci 2011; 45: 350–353. 7. Tsutiya K. Clinical features of frontotemporal dementia. Clin Neurosci 2005; 23: 262–265. 8. Joseph KA, Hodges JR, Snowden JS et al. Neuropathological background of phenotypical variability in frontotemporal dementia. Acta Neuropathol 2011; 122: 137–153. 9. Cairns NJ, Ghoshal N. FUS: a new actor on the frontotemporal lober degeneration stage. Neurology 2010; 74: 354–356. 10. Dickson DW, Bergeron C, Chin SS et al. Office of Rare Diseases neuropathologic criteria for corticobasal degeneration. J Neuropathol Exp Neurol 2002; 61: 935– 946. 11. Wakabayashi K, Takahashi H. Pathological heterogeneity in progressive superanuclear palsy and corticobasal degeneration. Neuropathology 2004; 24: 79–86. 12. Ikeda K, Akiyama H, Haga C et al. Argyrophilic threads-like structure in corticobasal degeneration and superanuclear palsy. Neurosci Lett 1994; 174: 157–159. 13. Kouri N, Whitwell JL, Josephs KA, Rademakers R, Dickson DW. Corticobasal degeneration: a pathologically distinct 4R tauopathy. Nat Rev Neurol 2011; 7: 263–272. 14. Saito Y, Kawashima A, Ruberu NN et al. Accumulation of phosphorylated alpha-synuclein in aging human brian. J Neuropathol Exp Neurol 2003; 62: 644– 654. 15. De Silva R, Lashley T, Gibb G et al. Pathological inclusion bodies in tauopathies contain distinct complements of tau with three or four microtubule-binding repeat domains as demonstrated by new specific monoclonal antibodies. Neuropathol Appl Neurobiol 2003; 29: 288–302. 16. Togo T, Sahara N, Yen SH et al. Argyrophilic grain disease is a sporadic 4-repeat tauopathy. J Neuropathol Exp Neurol 2002; 61: 547–556. 17. Uchihara T, Nakamura A, Shibuya K, Yagishita S. Specific detection of pathological three-repeat tau after

© 2014 Japanese Society of Neuropathology

9

18.

19.

20.

21.

22.

23.

24.

25.

26. 27.

28.

pretreatment with potassium permanganate and oxalic acid in PSP/CBD brains. Brain Pathol 2011; 21: 180– 188. Mizuno Y, Ozeki M, Iwata H et al. A case of clinically and neuropathologically atypical corticobasal degeneration with widespread iron deposition. Acta Neuropathol 2002; 103: 288–294. Wakabayashi K, Mori F, Hasegawa M et al. Co-localization of beta-peptide and phosphorylated tau in astrocytes in a patient with corticobasal degeneration. Neuropathology 2006; 26: 66–71. Zhang W, Zheng R, Wang Z, Yuan Y. The overlap of corticobasal degeneration and Alzheimer changes: an autopsy case. Neuropathology 2009; 29: 720–726. Homma T, Bandoh M, Mochizuki Y et al. An autopsy case of corticobasal degeneration with notable early onset apraxia: a case report and literature review focused on apraxia. Brain Nerve 2013; 65: 887–893. Armstrong MJ, Litvan I, Lang AE et al. Criteria for the diagnosis of corticobasal degeneration. Neurology 2013; 80: 496–503. Dickson D, Litvan I. Corticobasal degeneration. In: Dickson DW, ed. Neurodgeneration: The Molecular Pathology of Dementia and Movement Disorders. Basel: ISN Neuropath Press, 2003; 115–123. Tan CF, Piao YS, Kakita A et al. Frontotemporal dementia with co-occurrence of astrocytic plaques and tufted astrocytes, and severe degeneration of the cerebral white matter: a variant of corticobasal degeneration? Acta Neuropathol 2005; 109: 329–338. Ohara S, Tsuyazaki J, Oide T et al. A clinical and neuropathological study of an unusual case of sporadic tauopathy. A variant of corticobasal degeneration. Neurosci Lett 2002; 330: 84–88. Yoshida M. Neuropathology of tauopathy. Brain Nerve 2013; 65: 1445–1458. Arai T, Ikeda K, Akiyama H, Tsutiya K, Yagishita S, Takamatsu J. Intracellular processing of aggregated tau differs between corticobasal degeneration and progressive supranuclear palsy. Neuroreport 2001; 12: 935– 938. Iseki E, Yamamoto R, Murayama N et al. Immunohistochemical investigation of neurofibrillary tangles and their tau isoforms in brains of limbic neurofibrillary tangle dementia. Neurosci Lett 2006; 405: 29–33.

An autopsied case of corticobasal degeneration showing severe cerebral atrophy over a protracted disease course of 16 years.

The patient was a 72-year-old Japanese woman. At the age of 57, she started having difficulty performing daily work and developed agraphia. She also e...
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