Pathologie und Biochemie der frontotemporalen Demenzen

M. Neumann; H. A. Kretzschmar

doi:10.1055/s-0038-1626278

Nervenheilkunde, Inhaltsverzeichnis

Nervenheilkunde 2004; 23(02): 73-79
DOI: 10.1055/s-0038-1626278

Original- und Übersichtsarbeiten - Original and Review Articles

Schattauer GmbH

Pathologie und Biochemie der frontotemporalen Demenzen

Pathology and biochemistry of frontotemporal dementias

M. Neumann

¹Zentrum für Neuropathologie und Prionforschung, Ludwig-Maximilians-Universität München

,

H. A. Kretzschmar

¹Zentrum für Neuropathologie und Prionforschung, Ludwig-Maximilians-Universität München

› Institutsangaben

Abstract

Zusammenfassung

Unter dem klinischen Terminus frontotemporale Demenz (FTD) wird eine heterogene Gruppe neurodegenerativer Erkrankungen zusammengefasst. In den vergangenen Jahren sind die Erkenntnisse über genetische Ursachen und molekulare Mechanismen der FTD rasch vorangeschritten und haben einen Wandel der Klassifikation wie auch der Nomenklatur auf diesem Gebiet eingeleitet. Trotz Fortschritten in der klinischen Diagnostik ist eine Unterscheidung der einzelnen FTD-Entitäten derzeit nur durch eine neuropathologische Untersuchung des Gehirns möglich. Die gängige neuropathologische Klassifikation der FTD basiert auf der Morphologie sowie der histochemischen und biochemischen Charakterisierung von Einschlusskörperchen. Die Spezifizierung der Einschlüsse erfolgt hierbei mittels Antikörpern gegen Tau, Ubiquitin und Neurofilamente. Zur weiteren Erforschung der zugrunde liegenden molekularen Mechanismen der FTD insbesondere im Hinblick auf die Entwicklung neuer Therapien, sind Untersuchungen an Hirngewebe von klinisch und neuropathologisch gut dokumentierten Fällen dringend erforderlich. Einen wichtigen Beitrag hierzu können Hirngewebebanken, wie die Deutsche Hirngewebebank »Brain-Net«, leisten.

Summary

The clinical term frontotemporal dementia covers a heterogeneous group of neurodegenerative diseases. The increasing knowledge about genetic and molecular mechanisms involved in frontotemporal dementia (FTD) has led to a change of classification and nomenclature of FTD. In spite of the progress in the clinical diagnosis, a definite diagnosis and discrimination of the FTD entities to date is only possible by neuropathological examination of the brain. The current consensus on the pathological classification of FTD is based on the morphology and the histochemical and biochemical characterization of inclusion bodies. For the classification of inclusions antibodies against tau, ubiquitin and neurofilaments are used. To obtain further knowledge about the underlying molecular mechanisms in FTD, particularly with regard to new therapeutic strategies, studies with clinically and neuropathologically well-documented cases are essential. Brain banks, such as the German brain bank »Brain-Net«, may offer an important contribution to that.

Schlüsselwörter

Frontotemporale Demenz - Tau - Ubiquitin - Neuropathologie - Hirngewebebank

Keywords

Frontotemporal dementia - tau - ubiquitin - neuropathology - brain bank

Volltext

Referenzen

Literatur
1 Adamec E, Chang HT, Stopa EG, Hedreen JC, Vonsattel JP. Tau protein expression in frontotemporal dementias. Neurosci Lett 2001; 315 (1-2): 21-4.
2 Bergeron C, Davis A, Lang AE. Corticobasal ganglionic degeneration and progressive supranuclear palsy presenting with cognitive decline. Brain Pathol 1998; 08 (02) 355-65.
3 Brown J. Chromosome 3-linked frontotemporal dementia. Cell Mol Life Sci 1998; 54 (09) 925-7.
4 Buée L, Delacourte A. Comparative biochemistry of tau in progressive supranuclear palsy, corticobasal degeneration, FTDP-17 and Pick’s disease. Brain Pathol 1999; 09: 681-93.
5 Bugiani O, Murrell JR, Giaccone G, Hasegawa M, Ghigo G, Tabaton M, Morbin M, Primavera A, Carella F, Solaro C, Grisoli M, Savoiardo M, Spillantini MG, Tagliavini F, Goedert M, Ghetti B. Frontotemporal dementia and corticobasal degeneration in a family with a P301S mutation in tau. J Neuropathol Exp Neurol 1999; 58: 667-77.
6 Cairns NJ, Armstrong RA. Clustering of neuronal inclusions in “dementia with neurofilament inclusions”. Acta Neuropathol (Berl) 2003; 106 (02) 125-8.
7 Cairns NJ, Perry RH, Jaros E, Burn D, McKeith IG, Lowe JS, Holton J, Rossor MN, Skullerud K, Duyckaerts C, Cruz-Sanchez FF, Lantos PL. Patients with a novel neurofilamentopathy: dementia with neurofilament inclusions. Neurosci Lett 2003; 341 (03) 177-80.
8 Clark LN, Poorkaj P, Wszolek Z, Geschwind DH, Nasreddine ZS, Miller B, Li D, Payami H, Awert F, Markopoulou K, Andreadis A, D’Souza I, Lee VM, Reed L, Trojanowski JQ, Zhukareva V, Bird T, Schellenberg G, Wilhelmsen KC. Pathogenetic implications of mutations in the tau gene in pallido-ponto-nigral degeneration and related neurodegenerative disorders linked to chromosome 17. Proc Natl Acad Sci USA 1998; 95: 13103-7.
9 Cooper PN, Jackson M, Lennox G, Lowe J, Mann DMA. τ, ubiquitin, and αB-crystallin immunohistochemistry define the principle causes of degenerative frontotemporal dementia. Arch Neurol 1995; 52: 1011-5.
10 Delacourte A, Robitaille Y, Sergeant N, Buee L, Hof PR, Wattez A, Laroche-Cholette A, Mathieu J, Chagnon P, Gauvreau D. Specific pathological Tau protein variants characterize Pick’s disease. J Neuropathol Exp Neurol 1996; 55 (02) 159-68.
11 Delacourte A, Sergeant N, Wattez A, Gauvreau D, Robitaille Y. Vulnerable neuronal subsets in Alzheimer’s and Pick’s disease are distinguished by their tau isoform distribution and phosphorylation. Ann Neurol 1998; 43 (02) 193-204.
12 Dickson DW, Bergeron C, Chin SS, Duyckaerts C, Horoupian D, Ikeda K, Jellinger K, Lantos PL, Lippa CF, Mirra SS, Tabaton M, Vonsattel JP, Wakabayashi K, Litvan I. Office of Rare Diseases of the National Institutes of Health. Office of Rare Diseases neuropathologic criteria for corticobasal degeneration. J Neuropathol Exp Neurol 2002; 61 (11) 935-46.
13 D´Souza I, Poorkaj P, Hong M, Nochlin D, Lee H-S, Bird TD, Schellenberg GD. Missense and silent tau gene mutations cause frontotemporal dementia with parkinsonism-chromososme 17 type, by affecting multiple alternative RNA splicing regulatory elements. Proc Natl Acad Sci USA 1999; 96: 5598-603.
14 Feany MB, Dickson DW. Widespread cytoskeletal pathology characterizes corticobasal degeneration. Am J Pathol 1995; 146: 1388-96.
15 Forno LS, Langston JW, Herrick MK, Wilson JD, Murayama S. Ubiquitin-positive neuronal and tau 2-positive glial inclusions in frontotemporal dementia of motor neuron type. Acta Neuropathol (Berl) 2002; 103 (06) 599-606.
16 Goedert M, Spillantini MG, Jakes R, Rutherford D, Crowther RA. Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer’s disease. Neuron 1989; 03 (04) 519-26.
17 Goode BL, Feinstein SC. Identification of a novel microtubule binding and assembly domain in the developmentally regulated interrepeat region of tau. J Cell Biol 1994; 124 (05) 769-82.
18 Grimes DA, Lang AE, Bergeron CB. Dementia as the most common presentation of corticalbasal ganglionic degeneration. Neurology 1999; 53 (09) 1969-74.
19 Gydesen S, Brown JM, Brun A, Chakrabarti L, Gade A, Johannsen P, Rossor M, Thusgaard T, Grove A, Yancopoulou D, Spillantini MG, Fisher EM, Collinge J, Sorensen SA. Chromosome 3 linked frontotemporal dementia (FTD-3). Neurology 2002; 59 (10) 1585-94.
20 Hauw JJ, Daniel SE, Dickson D, Horoupian DS, Jellinger K, Lantos PL, McKee A, Tabaton M, Litvan I. Preliminary NINDS neuropathologic criteria for Steele-Richardson-Olszewski syndrome (progressive supranuclear palsy). Neurology 1994; 44: 2015-9.
21 Hosler BA, Siddique T, Sapp PC, Sailor W, Huang MC, Hossain A, Daube JR, Nance M, Fan C, Kaplan J, Hung WY, McKenna-Yasek D, Haines JL, Pericak-Vance MA, Horvitz HR, Brown Jr RH. Linkage of familial amyotrophic lateral sclerosis with frontotemporal dementia to chromosome 9q21-q22. JAMA 2000; 284 (13) 1664-9.
22 Hutton M, Lendon CL, Rizzu P, Baker M, Froelich S, Houlden H. et al. Association of missense and 5´splice-site mutations in tau with the inherited dementia FTDP-17. Nature 1998; 393: 702-705.
23 Ikeda K, Akiyama H, Iritani S, Kase K, Arai T, Niizato K, Kuroki N, Kosaka K. Corticobasal degeneration with primary progressive aphasia and accentuated cortical lesion in superior temporal gyrus: case report and review. Acta Neuropathol (Berl) 1996; 92 (05) 534-9.
24 Josephs KA, Holton JL, Rossor MN, Braendgaard H, Ozawa T, Fox NC, Petersen RC, Pearl GS, Ganguly M, Rosa P, Laursen H, Parisi JE, Waldemar G, Quinn NP, Dickson DW, Revesz T. Neurofilament inclusion body disease: a new proteinopathy?. Brain 2003; 126 (Pt 10): 2291-2303.
25 Kertesz A, Munoz DG, Hillis A. Preferred terminology. Ann Neurol 2003; 54 (Suppl. 05) S3-6.
26 Knopman DS, Mastri AR, Frey WH, Sung JH, Rustan T. Dementia lacking distinctive histologic features: a common nonAlzheimer degenerative dementia. Neurology 1990; 40 (02) 251-6.
27 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. Astrocytic plaques and tufts of abnormal fibers do not coexist in corticobasal degeneration and progressive supranuclear palsy. Acta Neuropathol (Berl) 1998; 96 (04) 401-8.
28 Lendon CL, Lynch T, Norton J, McKeel Jr DW, Busfield F, Craddock N, Chakraverty S, Gopalakrishnan G, Shears SD, Grimmett W, Wilhelmsen KC, Hansen L, Morris JC, Goate AM. Hereditary dysphasic disinhibition dementia. A frontotemporal dementia linked to 17q21-22. Neurology 1998; 50: 1546-55.
29 Litvan I, Agid Y, Calne D, Campbell G, Dubois B, Duvoisin RC, Goetz CG, Golbe LI, Grafman J, Growdon JH, Hallett M, Jankovic J, Quinn NP, Tolosa E, Zee DS. Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome): Report of the NINDS-SPSP International Workshop. Neurology 1996; 47: 1-9.
30 Mackenzie IR, Feldman H. The relationship between extramotor ubiquitin-immunoreactive neuronal inclusions and dementia in motor neuron disease. Acta Neuropathol (Berl) 2003; 105 (02) 98-102.
31 McKhann GM, Albert MS, Grossman M, Miller B, Dickson D, Trojanowski JQ. Clinical and pathological diagnosis of frontotemporal dementia: report of the Work Group on Frontotemporal Dementia and Pick’s Disease. Arch Neurol 2001; 58 (11) 1803-9.
32 Mirra SS, Murrell JR, Gearing M, Spillantini MG, Goedert M, Crowther RA, Levey AI, Jones R, Green J, Shoffner JM, Wainer BH, Schmidt ML, Trojanowski JQ, Ghetti B. Tau pathology in a family with dementia and a P301L mutation in tau. J Neuropathol Exp Neurol 1999; 58: 335-45.
33 Munoz DG, Dickson DW, Bergeron C, Mackenzie IR, Delacourte A, Zhukareva V. The neuropathology and biochemistry of frontotemporal dementia. Ann Neurol 2003; 54 (Suppl. 05) S 24-8.
34 Murrell JR, Spillantini MG, Zolo P, Guazzelli M, Smith MJ, Hasegawa M, Redi F, Crowther RA, Pietrini P, Ghetti B, Goedert M. Tau gene mutation G389R causes a tauopathy with abundant Pick body-like inclusions and axonal deposits. J Neuropathol Exp Neurol 1999; 58: 1207-26.
35 Neumann M, Schulz-Schaeffer W, Crowther RA, Smith MJ, Spillantini MG, Goedert M, Kretzschmar HA. Pick’s disease associated with the novel Tau gene mutation K369I. Ann Neurol 2001; 50 (04) 503-13.
36 Poorkaj P, Bird TD, Wijsman E, Nemens E, Garruto RM, Anderson L, Andreadis A, Wiederholt WC, Raskind M, Schellenberg GD. Tau is a candidate gene for chromosome 17 frontotemporal dementia. Ann Neurol 1998; 43 (06) 815-25.
37 Poorkaj P, Muma NA, Zhukareva V, Cochran EJ, Shannon KM, Hurtig H, Koller WC, Bird TD, Trojanowski JQ, Lee VM, Schellenberg GD. An R5L tau mutation in a subject with a progressive supranuclear palsy phenotype. Ann Neurol 2002; 52 (04) 511-6.
38 Rizzini C, Goedert M, Hodges JR, Smith MJ, Jakes R, Hills R, Xuereb JH, Crowther RA, Spillantini MG. Tau gene mutation K257T causes a tauopathy similar to Pick’s disease. J Neuropathol Exp Neurol 2000; 59 (11) 990-1001.
39 Rizzu P, Van Swieten JC, Joosse M, Hasegawa M, Stevens M, Tibben A, Niermeijer MF, Hillebrand M, Ravid R, Oostra BA, Goedert M, van Duijn CM, Heutink P. High prevalence of mutations in the microtubule-associated protein tau in a population study of frontotemporal dementia in the Netherlands. Am J Hum Genet 1999; 64: 414-421.
40 Rosso SM, Kamphorst W, de Graaf B, Willemsen R, Ravid R, Niermeijer MF. et al. Familial frontotemporal dementia with ubiquitin-positive inclusions is linked to chromosome 17q21-22. Brain 2001; 124 (Pt 10): 1948-57.
41 Rosso SM, van Herpen E, Deelen W, Kamphorst W, Severijnen LA, Willemsen R, Ravid R, Niermeijer MF, Dooijes D, Smith MJ, Goedert M, Heutink P, van Swieten JC. A novel tau mutation, S320F, causes a tauopathy with inclusions similar to those in Pick’s disease. Ann Neurol 2002; 51 (03) 373-6.
42 Shahani N, Brandt R. Functions and malfunctions of the tau proteins. Cell Mol Life Sci 2002; 59 (10) 1668-80.
43 Spillantini MG, Goedert M. Tau mutations in familial frontotemporal dementia. Brain 2000; 123 (Pt 5): 857-9.
44 Spillantini MG, Murrel JR, Goedert M, Farlow MR, Klug A, Ghetti B. Mutation in the tau gene in familial multiple system tauopathy withh presenile dementia. Proc Natl Acad Sci USA 1998; 95: 7737-41.
45 Spillantini MG, Yoshida H, Rizzini C, Lantos PL, Khan N, Rossor MN, Goedert M, Brown J. A novel tau mutation (N296N) in familial dementia with swollen achromatic neurons and corticobasal inclusion bodies. Ann Neurol 2000; 48 (06) 939-43.
46 Stanford PM, Halliday GM, Brooks WS, Kwok JB, Storey CE, Creasey H, Morris JG, Fulham MJ, Schofield PR. Progressive supranuclear palsy pathology caused by a novel silent mutation in exon 10 of the tau gene: expansion of the disease phenotype caused by tau gene mutations. Brain 2000; 123 (Pt 5): 880-93.
47 Steele J, Richardson J, Olszewski J. Progressive supranuclear palsy; a heterogeneous degeneration involving the brain stem, basal ganglia and cerebellum with vertical gaze and pseudobulbar palsy, nuclear dystonia and dementia. Archives of Neurology 1964; 10: 333-59.
48 Woulfe J, Kertesz A, Munoz DG. Frontotemporal dementia with ubiquitinated cytoplasmic and intranuclear inclusions. Acta Neuropathol (Berl) 2001; 102 (01) 94-102.
49 Yasuda M, Takamatsu J, D’Souza I, Crowther RA, Kawamata T, Hasegawa M, Spillantini MG, Tanimukai S, Poorkaj P, Varani L, Varani G, Iwatsubo T, Goedert M, Schellenberg DG, Tanaka C. A novel mutation at position +12 in the intron following exon 10 of the tau gene in familial frontotemporal dementia (FTDKumamoto). Ann Neurol 2000; 47 (04) 422-9.
50 Zhukareva V, Mann D, Pickering-Brown S, Uryu K, Shuck T, Shah K, Grossman M, Miller BL, Hulette CM, Feinstein SC, Trojanowski JQ, Lee VM. Sporadic Pick’s disease: a tauopathy characterized by a spectrum of pathological tau isoforms in gray and white matter. Ann Neurol 2002; 51 (06) 730-9.
51 Zhukareva V, Sundarraj S, Mann D, Sjogren M, Blenow K, Clark CM, McKeel DW, Goate A, Lippa CF, Vonsattel JP, Growdon JH, Trojanowski JQ, Lee VM. Selective reduction of soluble tau proteins in sporadic and familial frontotemporal dementias: an international follow-up study. Acta Neuropathol (Berl) 2003; 105 (05) 469-76.
52 Zhukareva V, Vogelsberg-Ragaglia V, Van Deerlin VM, Bruce J, Shuck T, Grossman M, Clark CM, Arnold SE, Masliah E, Galasko D, Trojanowski JQ, Lee VM. Loss of brain tau defines novel sporadic and familial tauopathies with frontotemporal dementia. Ann Neurol 2001; 49 (02) 165-75.