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Open Access 01-10-2007 | Original Paper

Argyrophilic thorny astrocyte clusters in association with Alzheimer’s disease pathology in possible primary progressive aphasia

Authors: David G. Munoz, John Woulfe, Andrew Kertesz

Published in: Acta Neuropathologica | Issue 4/2007

Abstract

Although most cases of primary progressive aphasia (PPA) have one of the varieties of frontotemporal lobar degeneration (FTLD) as their pathological substrate, a subset shows Alzheimer’s disease (AD) pathology. We report that all eight cases in our clinic diagnosed as possible PPA, on account of the presence of episodic memory difficulties in addition to severe language impairment at the onset of disease, showed AD pathology. Neither focal accentuation of AD pathology nor vascular lesions in language-related areas was observed. Seven of these eight patients showed large argyrophilic thorny astrocyte clusters (ATAC) in the fronto-temporo-parietal cortex and subcortical white matter. The intensely tau immunoreactive astrocytes in ATAC were morphologically similar to the perivascular, subpial, and subependymal astrocytes in elderly brains, but ATAC differ from the latter by the cortical and subcortical location, widespread distribution outside the medial temporal lobe, and intense argyrophilia. The location of ATAC was related to neither local variations in the load of AD pathology, nor the myelin density of white matter. ATAC were not seen in a comparison group of six cases of AD without a prominent aphasia syndrome. Because of the similarity of astrocytes in ATAC to those seen independently of AD pathology in several subtypes of FTLD and two reported cases of PPA we hypothesize that they are a marker of a pathological process concurrent with AD, and related to the focality of the clinical presentation.

Appell J, Kertesz A, Fisman M (1982) A study of language functioning in Alzheimer patients. Brain Lang 17:73–91PubMedCrossRef

Bergeron C, Pollanen MS, Weyer L, Lang AE (1997) Cortical degeneration in progressive supranuclear palsy. A comparison with cortical-basal ganglionic degeneration. J Neuropathol Exp Neurol 56:726–734PubMed

Boeve B, Dickson D, Duffy J, Bartleson J, Trenerry M, Petersen R (2003) Progressive nonfluent aphasia and subsequent aphasic dementia associated with atypical progressive supranuclear palsy pathology. Eur Neurol 49:72–78PubMedCrossRef

Braak H, Braak E (1989) Cortical and subcortical argyrophilic grains characterize a disease associated with adult onset dementia. Neuropathol Appl Neurobiol 15:13–26PubMed

Cairns NJ, Bigio EH, Mackenzie IR, Neumann M, Lee VM, Hatanpaa KJ, White CL III, Schneider JA, Grinberg LT, Halliday G, Duyckaerts C, Lowe JS, Holm IE, Tolnay M, Okamoto K, Yokoo H, Murayama S, Woulfe J, Munoz DG, Dickson DW, Ince PG, Trojanowski JQ, Mann DM (2007) Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the Consortium for Frontotemporal Lobar Degeneration. Acta Neuropathol (Berl) 114:5–22CrossRef

Delacourte A, Sergeant N, Wattez A, Robitaille I (1998) The biochemistry of the cytoskeleton in Pick complex. In: Kertesz A, Munoz DG (eds) Pick’s disease and Pick complex. Wiley-Liss, New York, pp 243–258

Deruaz JP, Assal G, Peter-Favre C (1993) Un cas clinicopathologique d’aphasie progressive. Rev Neurol (Paris) 149:186–191

Feany MB, Dickson DW (1995) Widespread cytoskeletal pathology characterizes corticobasal degeneration. Am J Pathol 146:1388–1396PubMed

Ferrer I, Hernandez I, Boada M, Llorente A, Rey MJ, Cardozo A, Ezquerra M, Puig B (2003) Primary progressive aphasia as the initial manifestation of corticobasal degeneration and unusual tauopathies. Acta Neuropathol (Berl) 106:419–435CrossRef

10.

Galton CJ, Patterson K, Xuereb JH, Hodges JR (2000) Atypical and typical presentations of Alzheimer’s disease: a clinical, neuropsychological, neuroimaging and pathological study of 13 cases. Brain 123:484–498PubMedCrossRef

11.

Ghetti B, Hutton ML, Wszolek ZK (2003) Frontotemporal dementia and parkinsonism linked to chromosome 17 associated with tau gene mutations (FTDP-17T). In: Dickson DW (ed) Neurodegeneration: the molecular pathology of dementia of movement disorders, Basel

12.

Goedert M, Jakes R, Vanmechelen E (1995) Monoclonal antibody AT8 recognises tau protein phosphorylated at both serine 202 and threonine 205. Neurosci Lett 189:167–169PubMedCrossRef

13.

Gorno-Tempini ML, Dronkers NF, Rankin KP, Ogar JM, Phengrasamy L, Rosen HJ, Johnson JK, Weiner MW, Miller BL (2004) Cognition and anatomy in three variants of primary progressive aphasia. Ann Neurol 55:335–346PubMedCrossRef

14.

Graff-Radford NR, Damasio AR, Hyman BT, Hart MN, Tranel D, Damasio H, Van Hoesen GW, Rezai K (1990) Progressive aphasia in a patient with Pick’s disease: a neuropsychological, radiologic, and anatomic study. Neurology 40:620–626PubMed

15.

Green J, Morris JC, Sandson J, McKeel DWJ, Miller JW (1990) Progressive aphasia: a precursor of global dementia? Neurology 40:423–429PubMed

16.

Greene JD, Patterson K, Xuereb J, Hodges JR (1996) Alzheimer disease and nonfluent progressive aphasia. Arch Neurol 53:1072–1078PubMed

17.

Harasty JA, Halliday GM, Xuereb J, Croot K, Bennett H, Hodges JR (2001) Cortical degeneration associated with phonologic and semantic language impairments in AD. Neurology 56:944–950PubMed

18.

Hashimoto N, Takeuchi T, Ishihara R, Ukai K, Kobayashi H, Iwata H, Iwai K, Mizuno Y, Yamaguchi H, Shibayama H (2003) Glial fibrillary tangles in diffuse neurofibrillary tangles with calcification. Acta Neuropathol (Berl) 106:150–156CrossRef

19.

Hauw JJ, Verny M, Delaere P, Cervera P, He Y, Duyckaerts C (1990) Constant neurofibrillary changes in the neocortex in progressive supranuclear palsy. Basic differences with Alzheimer’s disease and aging. Neurosci Lett 119:182–186PubMedCrossRef

20.

Holland AL, McBurney DH, Moossy J, Reinmuth OM (1985) The dissolution of language in Pick’s disease with neurofibrillary tangles: a case study. Brain Lang 24:36–58PubMedCrossRef

21.

Hyman BT, Trojanowski JQ (1997) Consensus recommendations for the postmortem diagnosis of Alzheimer disease from the National Institute on Aging and the Reagan Institute Working Group on diagnostic criteria for the neuropathological assessment of Alzheimer disease. J Neuropathol Exp Neurol 56:1095–1097PubMed

22.

Ikeda K, Akiyama H, Arai T, Nishimura T (1998) Glial tau pathology in neurodegenerative diseases: their nature and comparison with neuronal tangles. Neurobiol Aging 19:S85–S91PubMedCrossRef

23.

Ikeda K, Akiyama H,.Kondo H (1993) Anti-tau-positive glial fibrillary tangles in the brain of postencephalitic parkinsonism of Economo type. Neurosci Lett 162:176–178PubMedCrossRef

24.

Ikeda K, Akiyama H, Kondo H, Arai T, Arai N,Yagishita S (1995) Numerous glial fibrillary tangles in oligodendroglia in cases of subacute sclerosing panencephalitis with neurofibrillary tangles. Neurosci Lett 194:133–135PubMedCrossRef

25.

Ikeda K, Akiyama H, Kondo H, Haga C (1995) A study of dementia with argyrophilic grains. Possible cytoskeletal abnormality in dendrospinal portion of neurons and oligodendroglia. Acta Neuropathol (Berl) 89:409–414CrossRef

26.

Ikeda K, Akiyama H, Kondo H, Haga C, Tanno E, Tokuda T, Ikeda S (1995) Thorn-shaped astrocytes: possibly secondarily induced tau-positive glial fibrillary tangles. Acta Neuropathol (Berl) 90:620–625

27.

Iwasaki Y, Yoshida M, Hattori M, Goto A, Aiba I, Hashizume Y, Sobue G (2004) Distribution of tuft-shaped astrocytes in the cerebral cortex in progressive supranuclear palsy. Acta Neuropathol (Berl) 108:399–405CrossRef

28.

Iwatsubo T, Hasegawa M, Ihara Y (1994) Neuronal and glial tau-positive inclusions in diverse neurologic diseases share common phosphorylation characteristics. Acta Neuropathol (Berl) 88:129–136

29.

Kertesz A (1980) Western aphasia battery. San Antonio, TX, The Psychological Corporation. (GENERIC) Ref Type: Generic

30.

Kertesz A, Davidson W, McCabe P, Takagi K, Munoz D (2003) Primary progressive aphasia: diagnosis, varieties, evolution. J Int Neuropsychol Soc 9:710–719PubMedCrossRef

31.

Kertesz A, Hudson L, Mackenzie IR, Munoz DG (1994) The pathology and nosology of primary progressive aphasia. Neurology 44:2065–2072PubMed

32.

Kertesz A, McMonagle P, Blair M, Davidson W, Munoz DG (2005) The evolution and pathology of frontotemporal dementia. Brain 128:1996–2005PubMedCrossRef

33.

Kertesz A, Munoz DG (2002) Primary progressive aphasia: a review of the neurobiology of a common presentation of Pick complex. Am J Alzheimers Dis Other Demen 17:30–36PubMedCrossRef

34.

Kinoshita A, Tomimoto H, Tachibana N, Suenaga T, Kawamata T, Kimura T, Akiguchi I, Kimura J (1996) A case of primary progressive aphasia with abnormally ubiquitinated neurites in the cerebral cortex. Acta Neuropathol (Berl) 92:520–524CrossRef

35.

Kirshner HS, Tanridag O, Thurman L,Whetsell WO Jr (1987) Progressive aphasia without dementia: two cases with focal spongiform degeneration. Ann Neurol 22:527–532PubMedCrossRef

36.

Knibb JA, Xuereb JH, Patterson K, Hodges JR (2006) Clinical and pathological characterization of progressive aphasia. Ann Neurol 59:156–165PubMedCrossRef

37.

Komori T (1999) Tau-positive glial inclusions in progressive supranuclear palsy, corticobasal degeneration and Pick’s disease. Brain Pathol 9:663–679PubMedCrossRef

38.

Komori T, Arai N, Oda M, Nakayama H, Mori H, Yagishita S, Takahashi T, Amano N, Murayama S, Murakami S, Shibata N, Kobayashi M, Sasaki S, Iwata M (1998) Astrocytic plaques and tufts of abnormal fibers do not coexist in corticobasal degeneration and progressive supranuclear palsy. Acta Neuropathol (Berl) 96:401–408CrossRef

39.

Lippa CF, Cohen R, Smith TW, Drachman DA (1991) Primary progressive aphasia with focal neuronal achromasia. Neurology 41:882–886PubMed

40.

Manlow A, Munoz DG (1992) A non-toxic method for the demonstration of gliosis. J Neuropathol Exp Neurol 51:298–302PubMed

41.

Martinez-Lage P, Munoz DG (1997) Prevalence and disease associations of argyrophilic grains of Braak. J Neuropathol Exp Neurol 56:157–164PubMed

42.

McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (1984) Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 34:939–944PubMed

43.

McKhann GM, Albert MS, Grossman M, Miller B, Dickson D, Trojanowski JQ (2001) Clinical and pathological diagnosis of frontotemporal dementia: report of the Work Group on Frontotemporal Dementia and Pick’s Disease. Arch Neurol 58:1803–1809PubMedCrossRef

44.

Mehler MF, Horoupian DS, Davies P, Dickson DW (1987) Reduced somatostatin-like immunoreactivity in cerebral cortex in nonfamilial dysphasic dementia. Neurology 37:1448–1453PubMed

45.

Mesulam MM (1982) Slowly progressive aphasia without generalized dementia. Ann Neurol 11:592–598PubMedCrossRef

46.

Mesulam MM (2001) Primary progressive aphasia. Ann Neurol 49:425–432PubMedCrossRef

47.

Mirra SS, Heyman A, McKeel D, Sumi SM, Crain BJ, Brownlee LM, Vogel FS, Hughes JP, van-Belle G, Berg L (1991) The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer’s disease. Neurology 41:479–486PubMed

48.

Mochizuki A, Ueda Y, Komatsuzaki Y, Tsuchiya K, Arai T, Shoji S (2003) Progressive supranuclear palsy presenting with primary progressive aphasia—clinicopathological report of an autopsy case. Acta Neuropathol (Berl) 105:610–614

49.

Molina JA, Probst A, Villanueva C, Jimenez-Jimenez FJ, Madero S, Torres N, Bermejo F (1998) Primary progressive aphasia with glial cytoplasmic inclusions. Eur Neurol 40:71–77PubMedCrossRef

50.

Munoz DG (1999) Stains for the differential diagnosis of degenerative dementias. Biotech Histochem 74:311–320PubMed

51.

Munoz DG, Dickson DW, Bergeron C, Mackenzie IR, Delacourte A, Zhukareva V (2003) The neuropathology and biochemistry of frontotemporal dementia. Ann Neurol 54:S24–S28PubMedCrossRef

52.

Munoz DG, Kertesz A (2001) The neuropathology of primary progressive aphasia. Neurology 56(Suppl 3):A178 (Abstract)

53.

Munoz DG, Woulfe J, Rabano A, Gerrero C, Kertesz A (2003) Glial Tau pathology as the specific structural correlate of focal presentation of Alzheimer’s disease. Neurology 60(Suppl 1):A312 (Abstract)

54.

Nishimura M, Namba Y, Ikeda K, Oda M (1992) Glial fibrillary tangles with straight tubules in the brains of patients with progressive supranuclear palsy. Neurosci Lett 143:35–38PubMedCrossRef

55.

Nishimura T, Ikeda K, Akiyama H, Arai T, Kondo H, Okochi M, Furiya Y, Mori H, Oda T, Kato M, Iseki E (1997) Glial tau-positive structures lack the sequence encoded by exon 3 of the tau protein gene. Neurosci Lett 224:169–172PubMedCrossRef

56.

Pogacar S, Williams RS (1984) Alzheimer’s disease presenting as slowly progressive aphasia. R I Med J 67:181–185PubMed

57.

Scheltens P, Ravid R, Kamphorst W (1994) Pathologic findings in a case of primary progressive aphasia. Neurology 44:279–282PubMed

58.

Schultz C, Ghebremedhin E, Del Tredici K, Rub U, Braak H (2004) High prevalence of thorn-shaped astrocytes in the aged human medial temporal lobe. Neurobiol Aging 25:397–405PubMedCrossRef

59.

Schwarz M, De BR, Poeck K, Weis J (1998) A case of primary progressive aphasia. A 14-year follow-up study with neuropathological findings. Brain 121:115–126PubMedCrossRef

60.

Shi J, Shaw CL, Du PD, Richardson AM, Bailey KL, Julien C, Stopford C, Thompson J, Varma A, Craufurd D, Tian J, Pickering-Brown S, Neary D, Snowden JS, Mann DM (2005) Histopathological changes underlying frontotemporal lobar degeneration with clinicopathological correlation. Acta Neuropathol (Berl) 110:501–512CrossRef

61.

Snowden JS, Neary D, Mann DM, Goulding PJ, Testa HJ (1992) Progressive language disorder due to lobar atrophy. Ann Neurol 31:174–183PubMedCrossRef

62.

Togo T, Dickson DW (2002) Tau accumulation in astrocytes in progressive supranuclear palsy is a degenerative rather than a reactive process. Acta Neuropathol (Berl) 104:398–402CrossRef

63.

Wakabayashi K, Oyanagi K, Makifuchi T, Ikuta F, Homma A, Homma Y, Horikawa Y,Tokiguchi S (1994) Corticobasal degeneration: etiopathological significance of the cytoskeletal alterations. Acta Neuropathol (Berl) 87:545–553

64.

Wakabayashi K, Shibasaki Y, Hasegawa M, Horikawa Y, Soma Y, Hayashi S, Morita T, Iwatsubo T, Takahashi H (2000) Primary progressive aphasia with focal glial tauopathy. Neuropathol Appl Neurobiol 26:477–481PubMedCrossRef

65.

Watanabe N, Takio K, Hasegawa M, Arai T, Titani K, Ihara Y (1992) Tau 2: a probe for a Ser conformation in the amino terminus of tau. J Neurochem 58:960–966PubMedCrossRef

66.

Wechsler AF, Verity MA, Rosenschein S, Fried I, Scheibel AB (1982) Pick’s disease. A clinical, computed tomographic, and histologic study with golgi impregnation observations. Arch Neurol 39:287–290PubMed

67.

Yamada T, Calne DB, Akiyama H, McGeer EG, McGeer PL (1993) Further observations on Tau-positive glia in the brains with progressive supranuclear palsy. Acta Neuropathol (Berl) 85:308–315

68.

Yamada T, McGeer PL (1990) Oligodendroglial microtubular masses: an abnormality observed in some human neurodegenerative diseases. Neurosci Lett 120:163–166PubMedCrossRef

69.

Yamada T, McGeer PL, McGeer EG (1992) Appearance of paired nucleated, Tau-positive glia in patients with progressive supranuclear palsy brain tissue. Neurosci Lett 135:99–102PubMedCrossRef

70.

Yamazaki M, Nakano I, Imazu O, Terashi A (1995) Paired helical filaments and straight tubules in astrocytes: an electron microscopic study in dementia of the Alzheimer type. Acta Neuropathol (Berl) 90:31–36

71.

Yasuhara O, Matsuo A, Tooyama I, Kimura H, McGeer EG, McGeer PL (1995) Pick’s disease immunohistochemistry: new alterations and Alzheimer’s disease comparisons. Acta Neuropathol (Berl) 89:322–330

Title: Argyrophilic thorny astrocyte clusters in association with Alzheimer’s disease pathology in possible primary progressive aphasia
Authors: David G. Munoz
John Woulfe
Andrew Kertesz
Publication date: 01-10-2007
Publisher: Springer-Verlag
Published in: Acta Neuropathologica / Issue 4/2007
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-007-0266-x

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Argyrophilic thorny astrocyte clusters in association with Alzheimer’s disease pathology in possible primary progressive aphasia

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