Abstract
Intracellular deposition of hyperphosphorylated tau characterizes tauopathies: there is a spectrum from neuron-predominant through mixed neuronal and glial, to glia-predominant forms. However, tau pathology appears in practically all forms of human prion disease. In addition to the rare cooccurrence of a primary tauopathy with prion disease, tau pathology may associate with prion diseases in distinct patterns: (1) small neuritic profiles correlating with tissue lesioning can be observed in all prion diseases; (2) larger dystrophic neurites may be observed around PrP amyloid plaques; and (3) neurofibrillary degeneration may follow the distribution described by Braak and Braak as Alzheimer-related pathology but might show atypical locations. It may be associated with prominent neuropil threads in subcortical regions in certain mutations with Creutzfeldt–Jakob disease (i.e., E200K mutation). Furthermore, widespread neurofibrillary degeneration in several subcortical, allocortical, and neocortical regions is consistently associated with certain PRNP mutations in Gerstmann–Sträussler–Scheinker disease or PrP cerebral amyloid angiopathy. Other types of tau pathologies include the rare presence of glial tau immunoreactivity. In summary, widespread application of phospho-tau immunostaining has revealed a previously underrecognized spectrum of tau pathologies in human prion diseases. The relation between tau pathology and PrP deposition, and factors influencing its appearance in prion diseases merit further studies.
Keywords
- Alzheimer disease
- Argyrophilic grain disease
- Cerebral amyloid angiopathy
- Corticobasal degeneration
- Creutzfeldt–Jakob disease
- Dementia with Lewy bodies
- Fatal familial insomnia
- Gerstmann–Sträussler–Scheinker disease
- Glycogen synthase kinase 3β
- Neurodegenerative disease
- Neurofibrillary tangle
- Prion protein
- Prion protein gene
- Progressive supranuclear palsy
- Proteinase K
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Abbreviations
- AD:
-
Alzheimer disease
- AGD:
-
Argyrophilic grain disease
- CAA:
-
Cerebral amyloid angiopathy
- CBD:
-
Corticobasal degeneration
- CJD:
-
Creutzfeldt–Jakob disease
- DLB:
-
Dementia with Lewy bodies
- FFI:
-
Fatal familial insomnia
- gCJD:
-
Genetic CJD
- GSK3β:
-
Glycogen synthase kinase 3β
- GSS:
-
Gerstmann–Sträussler–Scheinker disease
- iCJD:
-
iatrogenic CJD
- NDD:
-
Neurodegenerative disease
- NFT:
-
Neurofibrillary tangle
- PD:
-
Parkinson’s disease
- PK:
-
Proteinase K
- PRNP:
-
Prion protein gene
- PrP:
-
Prion protein
- PSP:
-
Progressive supranuclear palsy
- sCJD:
-
Sporadic CJD
- vCJD:
-
Variant CJD
References
Andreadis A, Brown WM, Kosik KS (1992) Structure and novel exons of the human tau gene. Biochemistry 31:10626–10633
Bancher C, Brunner C, Lassmann H et al (1989a) Tau and ubiquitin immunoreactivity at different stages of formation of Alzheimer neurofibrillary tangles. Prog Clin Biol Res 317:837–848
Bancher C, Brunner C, Lassmann H et al (1989b) Accumulation of abnormally phosphorylated tau precedes the formation of neurofibrillary tangles in Alzheimer’s disease. Brain Res 477:90–99
Bigio EH, Lipton AM, Yen SH et al (2001) Frontal lobe dementia with novel tauopathy: sporadic multiple system tauopathy with dementia. J Neuropathol Exp Neurol 60:328–341
Botez G, Probst A, Ipsen S, Tolnay M (1999) Astrocytes expressing hyperphosphorylated tau protein without glial fibrillary tangles in argyrophilic grain disease. Acta Neuropathol 98:251–256
Braak H, Braak E (1991) Neuropathological staging of Alzheimer-related changes. Acta Neuropathol 82:239–259
Cairns NJ, Bigio EH, Mackenzie IR et al (2007) Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the Consortium for Frontotemporal Lobar Degeneration. Acta Neuropathol 114:5–22
Dickson DW, Rademakers R, Hutton ML (2007) Progressive supranuclear palsy: pathology and genetics. Brain Pathol 17:74–82
Gambetti P, Dong Z, Yuan J et al (2008) A novel human disease with abnormal prion protein sensitive to protease. Ann Neurol 63:697–708
Ghetti B, Tagliavini F, Masters CL et al (1989) Gerstmann-Straussler-Scheinker disease II. Neurofibrillary tangles and plaques with PrP-amyloid coexist in an affected family. Neurology 39:1453–1461
Ghetti B, Dlouhy SR, Giaccone G et al (1995) Gerstmann-Straussler-Scheinker disease and the Indiana kindred. Brain Pathol 5:61–75
Ghetti B, Piccardo P, Frangione B et al (1996a) Prion protein amyloidosis. Brain Pathol 6:127–145
Ghetti B, Piccardo P, Spillantini MG et al (1996b) Vascular variant of prion protein cerebral amyloidosis with tau-positive neurofibrillary tangles: the phenotype of the stop codon 145 mutation in PRNP. Proc Natl Acad Sci U S A 93:744–748
Ghetti B, Tagliavini F, Takao M, Bugiani O, Piccardo P (2003) Hereditary prion protein amyloidoses. Clin Lab Med 23: 65–85, viii
Ghetti B, Tagliavini F, Kovacs GG, Piccardo P (2011) Gerstmann–Sträussler–Scheinker Disease. In: Dickson DW, Weller RO (eds) Neurodegeneration: the molecular pathology of dementia and movement disorders, 2nd edn. Wiley-Blackwell, New Jersey
Ghoshal N, Cali I, Perrin RJ et al (2009) Codistribution of amyloid beta plaques and spongiform degeneration in familial Creutzfeldt-Jakob disease with the E200K-129M haplotype. Arch Neurol 66:1240–1246
Giaccone G, Tagliavini F, Verga L et al (1990) Neurofibrillary tangles of the Indiana kindred of Gerstmann-Straussler-Scheinker disease share antigenic determinants with those of Alzheimer disease. Brain Res 530:325–329
Giaccone G, Mangieri M, Capobianco R et al (2008) Tauopathy in human and experimental variant Creutzfeldt-Jakob disease. Neurobiol Aging 29:1864–1873
Goedert M (2005) Tau gene mutations and their effects. Mov Disord 20(Suppl 12):S45–52
Goedert M, Klug A, Crowther RA (2006) Tau protein, the paired helical filament and Alzheimer’s disease. J Alzheimers Dis 9:195–207
Hainfellner JA, Wanschitz J, Jellinger K, Liberski PP, Gullotta F, Budka H (1998) Coexistence of Alzheimer-type neuropathology in Creutzfeldt-Jakob disease. Acta Neuropathol 96:116–122
Head MW, Lowrie S, Chohan G, Knight R, Scoones DJ, Ironside JW (2010) Variably protease-sensitive prionopathy in a PRNP codon 129 heterozygous UK patient with co-existing tau, alpha synuclein and Abeta pathology. Acta Neuropathol 120:821–823
Höftberger R, Kovacs GG, Ströbel T, Budka H (2011) Genetic Creutzfeldt-Jakob disease in Austria: Novel mutations and phenotypes. Prion 5:32
Holton JL, Ghiso J, Lashley T et al (2001) Regional distribution of amyloid-Bri deposition and its association with neurofibrillary degeneration in familial British dementia. Am J Pathol 158:515–526
Ishizawa K, Komori T, Shimazu T et al (2002) Hyperphosphorylated tau deposition parallels prion protein burden in a case of Gerstmann-Straussler-Scheinker syndrome P102L mutation complicated with dementia. Acta Neuropathol (Berl) 104:342–350
Jansen C, Parchi P, Jelles B et al (2011a) The first case of Fatal Familial Insomnia (FFI) in the Netherlands: a patient from Egyptian descent with concurrent 4 repeat tau deposits. Neuropathol Appl Neurobiol 37:549–553
Jansen C, Voet W, Head MW et al (2011b) A novel seven-octapeptide repeat insertion in the prion protein gene (PRNP) in a Dutch pedigree with Gerstmann-Straussler-Scheinker disease phenotype: comparison with similar cases from the literature. Acta Neuropathol 121:59–68
Jeong BH, Jeon YC, Lee YJ et al (2010) Creutzfeldt-Jakob disease with the V203I mutation and M129V polymorphism of the prion protein gene (PRNP) and a 17 kDa prion protein fragment. Neuropathol Appl Neurobiol 36:558–563
Kawashima T, Doh-ura K, Iwaki T (1999) Argyrophilic grains in late-onset Creutzfeldt-Jakob diseased brain. Pathol Int 49:369–373
Kopke E, Tung YC, Shaikh S, Alonso AC, Iqbal K, Grundke-Iqbal I (1993) Microtubule-associated protein tau. Abnormal phosphorylation of a non-paired helical filament pool in Alzheimer disease. J Biol Chem 268:24374–24384
Kovacs GG, Budka H (2009a) Molecular pathology of human prion diseases. Int J Mol Sci 10:976–999
Kovacs GG, Budka H (2009b) Protein-based neuropathology and molecular classification of human neurodegenerative diseases. In: Ovadi J, Orosz F (eds) Protein folding and misfolding: neurodegenerative diseases. Springer, Netherlands, pp 251–272
Kovacs GG, Alafuzoff I, Al-Sarraj S et al (2008a) Mixed brain pathologies in dementia: the BrainNet Europe consortium experience. Dement Geriatr Cogn Disord 26:343–350
Kovacs GG, Majtenyi K, Spina S et al (2008b) White matter tauopathy with globular glial inclusions: a distinct sporadic frontotemporal lobar degeneration. J Neuropathol Exp Neurol 67:963–975
Kovacs GG, Botond G, Budka H (2010) Protein coding of neurodegenerative dementias: the neuropathological basis of biomarker diagnostics. Acta Neuropathol 119:389–408
Kovacs GG, Molnar K, Laszlo L et al (2011a) A peculiar constellation of tau pathology defines a subset of dementia in the elderly. Acta Neuropathol 122:205–222
Kovacs GG, Seguin J, Quadrio I et al (2011b) Genetic Creutzfeldt-Jakob disease associated with the E200K mutation: characterization of a complex proteinopathy. Acta Neuropathol 121:39–57
Ladogana A, Sanchez-Juan P, Mitrova E et al (2009) Cerebrospinal fluid biomarkers in human genetic transmissible spongiform encephalopathies. J Neurol 256:1620–1628
Lawson VA, Klemm HM, Welton JM et al (2011) Gene knockout of tau expression does not contribute to the pathogenesis of prion disease. J Neuropathol Exp Neurol 70:1036–1045
Lee VM, Goedert M, Trojanowski JQ (2001) Neurodegenerative tauopathies. Annu Rev Neurosci 24:1121–1159
Mirra SS, Heyman A, McKeel D et al (1991) The consortium to establish a registry for Alzheimer’s disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer’s disease. Neurology 41:479–486
Mohr M, Tranchant C, Steinmetz G, Floquet J, Grignon Y, Warter JM (1999) Gerstmann-Straussler-Scheinker disease and the French-Alsatian A117V variant. Clin Exp Pathol 47:161–175
Perez M, Rojo AI, Wandosell F, Diaz-Nido J, Avila J (2003) Prion peptide induces neuronal cell death through a pathway involving glycogen synthase kinase 3. Biochem J 372:129–136
Piccardo P, Dlouhy SR, Lievens PM et al (1998) Phenotypic variability of Gerstmann-Straussler-Scheinker disease is associated with prion protein heterogeneity. J Neuropathol Exp Neurol 57:979–988
Powers JM, Byrne NP, Ito M et al (2003) A novel leukoencephalopathy associated with tau deposits primarily in white matter glia. Acta Neuropathol 106:181–187
Preusser M, Strobel T, Gelpi E et al (2006) Alzheimer-type neuropathology in a 28 year old patient with iatrogenic Creutzfeldt-Jakob disease after dural grafting. J Neurol Neurosurg Psychiatry 77:413–416
Quadrio I, Perret-Liaudet A, Kovacs GG (2011) Molecular diagnosis of human prion disease. Expert Opin Med Diagn 5:291–306
Reiniger L, Lukic A, Linehan J et al (2011) Tau, prions and Abeta: the triad of neurodegeneration. Acta Neuropathol 121:5–20
Reynolds CH, Garwood CJ, Wray S et al (2008) Phosphorylation regulates tau interactions with Src homology 3 domains of phosphatidylinositol 3-kinase, phospholipase Cgamma1, Grb2, and Src family kinases. J Biol Chem 283:18177–18186
Roeber S, Krebs B, Neumann M et al (2005) Creutzfeldt-Jakob disease in a patient with an R208H mutation of the prion protein gene (PRNP) and a 17-kDa prion protein fragment. Acta Neuropathol (Berl) 109:443–448
Saito Y, Ruberu NN, Sawabe M et al (2004) Staging of argyrophilic grains: an age-associated tauopathy. J Neuropathol Exp Neurol 63:911–918
Sanchez-Juan P, Bishop MT, Green A et al (2007) No evidence for association between tau gene haplotypic variants and susceptibility to Creutzfeldt-Jakob disease. BMC Med Genet 8:77
Sergeant N, Delacourte A, Buee L (2005) Tau protein as a differential biomarker of tauopathies. Biochim Biophys Acta 1739:179–197
Sikorska B, Liberski PP, Sobow T, Budka H, Ironside JW (2009) Ultrastructural study of florid plaques in variant Creutzfeldt-Jakob disease: a comparison with amyloid plaques in kuru, sporadic Creutzfeldt-Jakob disease and Gerstmann-Straussler-Scheinker disease. Neuropathol Appl Neurobiol 35:46–59
Tsuchiya K, Yagishita S, Ikeda K et al (2004) Coexistence of CJD and Alzheimer’s disease: an autopsy case showing typical clinical features of CJD. Neuropathology 24:46–55
van Swieten J, Spillantini MG (2007) Hereditary frontotemporal dementia caused by Tau gene mutations. Brain Pathol 17:63–73
Wang XF, Dong CF, Zhang J et al (2008) Human tau protein forms complex with PrP and some GSS- and fCJD-related PrP mutants possess stronger binding activities with tau in vitro. Mol Cell Biochem 310:49–55
Wang GR, Shi S, Gao C et al (2010) Changes of tau profiles in brains of the hamsters infected with scrapie strains 263 K or 139 A possibly associated with the alteration of phosphate kinases. BMC Infect Dis 10:86
Williams DR, Holton JL, Strand C et al (2007) Pathological tau burden and distribution distinguishes progressive supranuclear palsy-parkinsonism from Richardson’s syndrome. Brain 130:1566–1576
Yamada M, Itoh Y, Inaba A et al (1999) An inherited prion disease with a PrP P105L mutation: clinicopathologic and PrP heterogeneity. Neurology 53:181–188
Yamazaki M, Oyanagi K, Mori O et al (1999) Variant Gerstmann-Straussler syndrome with the P105L prion gene mutation: an unusual case with nigral degeneration and widespread neurofibrillary tangles. Acta Neuropathol 98:506–511
Yoshida H, Terada S, Ishizu H et al (2010) An autopsy case of Creutzfeldt-Jakob disease with a V180I mutation of the PrP gene and Alzheimer-type pathology. Neuropathology 30:159–164
Zou WQ, Puoti G, Xiao X et al (2010) Variably protease-sensitive prionopathy: a new sporadic disease of the prion protein. Ann Neurol 68:162–172
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2013 Springer Science+Business Media New York
About this chapter
Cite this chapter
Kovacs, G.G., Budka, H. (2013). The Spectrum of Tau Pathology in Human Prion Disease. In: Zou, WQ., Gambetti, P. (eds) Prions and Diseases. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5338-3_7
Download citation
DOI: https://doi.org/10.1007/978-1-4614-5338-3_7
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4614-5337-6
Online ISBN: 978-1-4614-5338-3
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)