Skip to main content
Log in

PART, a distinct tauopathy, different from classical sporadic Alzheimer disease

  • Correspondence
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

References

  1. Bancher C, Jellinger KA (1994) Neurofibrillary tangle predominant form of senile dementia of Alzheimer type: a rare subtype in very old subjects. Acta Neuropathol 88:565–570

    Article  CAS  PubMed  Google Scholar 

  2. Bancher C, Egensperger R, Kosel S, Jellinger K, Graeber MB (1997) Low prevalence of apolipoprotein E epsilon 4 allele in the neurofibrillary tangle predominant form of senile dementia. Acta Neuropathol 94:403–409

    Article  CAS  PubMed  Google Scholar 

  3. Boluda S, Iba M, Zhang B, Raible KM, Lee VM, Trojanowski JQ (2015) Differential induction and spread of tau pathology in young PS19 tau transgenic mice following intracerebral injections of pathological tau from Alzheimer’s disease or corticobasal degeneration brains. Acta Neuropathol 129:221–237

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Bouras C, Hof PR, Giannakopoulos P, Michel JP, Morrison JH (1994) Regional distribution of neurofibrillary tangles and senile plaques in the cerebral cortex of elderly patients: a quantitative evaluation of a one-year autopsy population from a geriatric hospital. Cereb Cortex 4:138–150

    Article  CAS  PubMed  Google Scholar 

  5. Braak H, Thal DR, Ghebremedhin E, Del Tredici K (2011) Stages of the pathologic process in Alzheimer disease: age categories from 1 to 100 years. J Neuropathol Exp Neurol 70:960–969

    Article  CAS  PubMed  Google Scholar 

  6. Braak H, Del Tredici K (2014) Are cases with tau pathology occurring in the absence of Abeta deposits part of the AD-related pathological process? Acta Neuropathol 128:767–772

    Article  PubMed  Google Scholar 

  7. Brettschneider J, Del Tredici K, Lee VM, Trojanowski JQ (2015) Spreading of pathology in neurodegenerative diseases: a focus on human studies. Nat Rev Neurosci 16:109–120

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Clavaguera F, Akatsu H, Fraser G, Crowther RA, Frank S, Hench J, Probst A, Winkler DT, Reichwald J, Staufenbiel M, Ghetti B, Goedert M, Tolnay M (2013) Brain homogenates from human tauopathies induce tau inclusions in mouse brain. Proc Natl Acad Sci USA 110:9535–9540

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Crary JF, Trojanowski JQ, Schneider JA, Abisambra JF, Abner EL, Alafuzoff I, Arnold SE, Attems J, Beach TG, Bigio EH, Cairns NJ, Dickson DW, Gearing M, Grinberg LT, Hof PR, Hyman BT, Jellinger K, Jicha GA, Kovacs GG, Knopman DS, Kofler J, Kukull WA, Mackenzie IR, Masliah E, McKee A, Montine TJ, Murray ME, Neltner JH, Santa-Maria I, Seeley WW, Serrano-Pozo A, Shelanski ML, Stein T, Takao M, Thal DR, Toledo JB, Troncoso JC, Vonsattel JP, White CL 3rd, Wisniewski T, Woltjer RL, Yamada M, Nelson PT (2014) Primary age-related tauopathy (PART): a common pathology associated with human aging. Acta Neuropathol 128:755–766

    Article  CAS  PubMed  Google Scholar 

  10. Cupidi C, Capobianco R, Goffredo D, Marcon G, Ghetti B, Bugiani O, Tagliavini F, Giaccone G (2010) Neocortical variation of Abeta load in fully expressed, pure Alzheimer’s disease. J Alzheimers Dis 19:57–68

    PubMed  Google Scholar 

  11. Davis MY, Keene CD, Jayadev S, Bird T (2014) The co-occurrence of Alzheimer’s disease and Huntington’s disease: a neuropathological study of 15 elderly Huntington’s disease subjects. J Huntingtons Dis 3:209–217

    CAS  PubMed  Google Scholar 

  12. Dickson DW, Davies P, Bevona C, Van Hoeven KH, Factor SM, Grober E, Aronson MK, Crystal HA (1994) Hippocampal sclerosis: a common pathological feature of dementia in very old (≥80 years of age) humans. Acta Neuropathol 88:212–221

    Article  CAS  PubMed  Google Scholar 

  13. Duyckaerts C, Braak H, Brion JP, Buee L, Del Tredici K, Goedert M, Halliday G, Neumann M, Spillantini MG, Tolnay M, Uchihara T (2015) PART is part of Alzheimer disease. Acta Neuropathol. doi:10.1007/s00401-00015-01390-00407

  14. Elbaz A, Ross OA, Ioannidis JP, Soto-Ortolaza AI, Moisan F, Aasly J, Annesi G, Bozi M, Brighina L, Chartier-Harlin MC, Destee A, Ferrarese C, Ferraris A, Gibson JM, Gispert S, Hadjigeorgiou GM, Jasinska-Myga B, Klein C, Kruger R, Lambert JC, Lohmann K, van de Loo S, Loriot MA, Lynch T, Mellick GD, Mutez E, Nilsson C, Opala G, Puschmann A, Quattrone A, Sharma M, Silburn PA, Stefanis L, Uitti RJ, Valente EM, Vilarino-Guell C, Wirdefeldt K, Wszolek ZK, Xiromerisiou G, Maraganore DM, Farrer MJ (2011) Independent and joint effects of the MAPT and SNCA genes in Parkinson disease. Ann Neurol 69:778–792

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Garcia-Sierra F, Hauw JJ, Duyckaerts C, Wischik CM, Luna-Munoz J, Mena R (2000) The extent of neurofibrillary pathology in perforant pathway neurons is the key determinant of dementia in the very old. Acta Neuropathol 100:29–35

    Article  CAS  PubMed  Google Scholar 

  16. Ghebremedhin E, Schultz C, Thal DR, Rub U, Ohm TG, Braak E, Braak H (2001) Gender and age modify the association between APOE and AD-related neuropathology. Neurology 56:1696–1701

    Article  CAS  PubMed  Google Scholar 

  17. Hansen LA, Masliah E, Galasko D, Terry RD (1993) Plaque-only Alzheimer disease is usually the Lewy body variant, and vice versa. J Neuropathol Exp Neurol 52:648–654

    Article  CAS  PubMed  Google Scholar 

  18. Haroutunian V, Schnaider-Beeri M, Schmeidler J, Wysocki M, Purohit DP, Perl DP, Libow LS, Lesser GT, Maroukian M, Grossman HT (2008) Role of the neuropathology of Alzheimer disease in dementia in the oldest-old. Arch Neurol 65:1211–1217

    Article  PubMed Central  PubMed  Google Scholar 

  19. Hauw JJ, Vignolo P, Duyckaerts C, Beck H, Forette F, Henry JF, Laurent M, Piette F, Sachet A, Berthaux P (1986) Neuropathological study of 12 centenarians: the incidence of Alzheimer type senile dementia is not particularly increased in this group of very old patients. Rev Neurol (Paris) 142:107–115

    CAS  Google Scholar 

  20. Ikeda K, Akiyama H, Arai T, Sahara N, Mori H, Usami M, Sakata M, Mizutani T, Wakabayashi K, Takahashi H (1997) A subset of senile dementia with high incidence of the apolipoprotein E epsilon2 allele. Ann Neurol 41:693–695

    Article  CAS  PubMed  Google Scholar 

  21. Iseki E, Tsunoda S, Suzuki K, Takayama N, Akatsu H, Yamamoto T, Kosaka K (2002) Regional quantitative analysis of NFT in brains of non-demented elderly persons: comparisons with findings in brains of late-onset Alzheimer’s disease and limbic NFT dementia. Neuropathology 22:34–39

    Article  PubMed  Google Scholar 

  22. Jack CR Jr, Knopman DS, Weigand SD, Wiste HJ, Vemuri P, Lowe V, Kantarci K, Gunter JL, Senjem ML, Ivnik RJ, Roberts RO, Rocca WA, Boeve BF, Petersen RC (2012) An operational approach to National Institute on Aging-Alzheimer’s Association criteria for preclinical Alzheimer disease. Ann Neurol 71:765–775

    Article  PubMed Central  PubMed  Google Scholar 

  23. Jack CR Jr (2014) PART and SNAP. Acta Neuropathol 128:773–776

    Article  PubMed Central  PubMed  Google Scholar 

  24. Jack CR Jr, Wiste HJ, Weigand SD, Rocca WA, Knopman DS, Mielke MM, Lowe VJ, Senjem ML, Gunter JL, Preboske GM, Pankratz VS, Vemuri P, Petersen RC (2014) Age-specific population frequencies of cerebral beta-amyloidosis and neurodegeneration among people with normal cognitive function aged 50–89 years: a cross-sectional study. Lancet Neurol 13:997–1005

    Article  PubMed  Google Scholar 

  25. Janocko NJ, Brodersen KA, Soto-Ortolaza AI, Ross OA, Liesinger AM, Duara R, Graff-Radford NR, Dickson DW, Murray ME (2012) Neuropathologically defined subtypes of Alzheimer’s disease differ significantly from neurofibrillary tangle-predominant dementia. Acta Neuropathol 124:681–692

    Article  PubMed Central  PubMed  Google Scholar 

  26. Jayadev S, Leverenz JB, Steinbart E, Stahl J, Klunk W, Yu CE, Bird TD (2010) Alzheimer’s disease phenotypes and genotypes associated with mutations in presenilin 2. Brain 133:1143–1154

    Article  PubMed Central  PubMed  Google Scholar 

  27. Jellinger KA, Attems J (2007) Neurofibrillary tangle-predominant dementia: comparison with classical Alzheimer disease. Acta Neuropathol 113:107–117

    Article  CAS  PubMed  Google Scholar 

  28. Jellinger KA, Attems J (2012) Neuropathology and general autopsy findings in nondemented aged subjects. Clin Neuropathol 31:87–98

    Article  PubMed  Google Scholar 

  29. Jun G, Ibrahim-Verbaas CA, Vronskaya M, Lambert J-C, Chung J, Naj AC, Kunkle BW, Wang L-S, Bis JC, Bellenguez C, Harold D, Lunetta KL, Destefano AL, Grenier-Boley B, Sims R, Beecham GW, Smith AV, Chouraki V, Hamilton-Nelson KL, Ikram MA, Fievet N, Denning N, Martin ER, Schmidt H, Kamatani Y, Dunstan ML, Valladares O, Laza AR, Zelenika D, Ramirez A, Foroud TM, Choi S-H, Boland A, Becker T, Kukull WA, van der Lee SJ, Pasquier F, Cruchaga C, Beekly D, Fitzpatrick AL, Hanon O, Gill M, Barber R, Gudnason V, Campion D, Love S, Bennett DA, Amin N, Berr C, Tsolaki M, Buxbaum JD, Lopez OL, Deramecourt V, Fox NC, Cantwell LB, Tárraga L, Dufouil C, Hardy J, Crane PK, Eiriksdottir G, Hannequin D, Clarke R, Evans D, Mosley Jr. TH, Letenneur L, Brayne C, Maier W, De Jager P, Emilsson V, Dartigues J-F, Hampel H, Kamboh MI, de Bruijn RFAG, Tzourio C, Pastor P, Larson EB, Rotter JI, O’Donovan MC, Montine TJ, Nalls MA, Mead S, Reiman EM, Jonsson PV, Holmes C, George-Hyslop PS, Boada M, Passmore P, Wendland JR, Schmidt R, Morgan K, Winslow AR, Powell JF, Carasquillo M, Younkin SG, Jakobsdóttir J, Kauwe JSK, Wilhelmsen KC, Rujescu D, Nöthen MM, Hofman A, Jones L, Consortium I, Haines JL, Psaty BM, Van Broeckhoven C, Holmans P, Launer LJ, Mayeux R, Lathrop M, Goate AM, Escott-Price V, Seshadri S, Pericak-Vance MA, Amouyel P, Williams J, van Duijn CM, Schellenberg GD, Farrer LA (2015) A novel Alzheimer disease locus located near the gene encoding tau protein. Mol Psychiatry (in press)

  30. Kawakami I, Hasegawa M, Arai T, Ikeda K, Oshima K, Niizato K, Aoki N, Omi K, Higashi S, Hosokawa M, Hirayasu Y, Akiyama H (2014) Tau accumulation in the nucleus accumbens in tangle-predominant dementia. Acta Neuropathol Commun 2:40

    Article  PubMed Central  PubMed  Google Scholar 

  31. Knopman DS, Jack CR Jr, Wiste HJ, Weigand SD, Vemuri P, Lowe VJ, Kantarci K, Gunter JL, Senjem ML, Mielke MM, Roberts RO, Boeve BF, Petersen RC (2013) Brain injury biomarkers are not dependent on beta-amyloid in normal elderly. Ann Neurol 73:472–480

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Knopman DS (2014) beta-Amyloidosis and neurodegeneration in Alzheimer disease: who’s on first? Neurology 82:1756–1757

    Article  PubMed  Google Scholar 

  33. Medway C, Morgan K (2014) Review: the genetics of Alzheimer’s disease; putting flesh on the bones. Neuropathol Appl Neurobiol 40:97–105

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Mizutani T (1996) Pathological diagnosis of Alzheimer-type dementia for old–old and oldest-old patients. Pathol Int 46:842–854

    Article  CAS  PubMed  Google Scholar 

  35. Montine TJ, Phelps CH, Beach TG, Bigio EH, Cairns NJ, Dickson DW, Duyckaerts C, Frosch MP, Masliah E, Mirra SS, Nelson PT, Schneider JA, Thal DR, Trojanowski JQ, Vinters HV, Hyman BT (2012) National Institute on Aging-Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease: a practical approach. Acta Neuropathol 123:1–11

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. Murray ME, Graff-Radford NR, Ross OA, Petersen RC, Duara R, Dickson DW (2011) Neuropathologically defined subtypes of Alzheimer’s disease with distinct clinical characteristics: a retrospective study. Lancet Neurol 10:785–796

    Article  PubMed Central  PubMed  Google Scholar 

  37. Nelson PT, Abner EL, Schmitt FA, Kryscio RJ, Jicha GA, Santacruz K, Smith CD, Patel E, Markesbery WR (2009) Brains with medial temporal lobe neurofibrillary tangles but no neuritic amyloid plaques are a diagnostic dilemma but may have pathogenetic aspects distinct from Alzheimer disease. J Neuropathol Exp Neurol 68:774–784

    Article  PubMed Central  PubMed  Google Scholar 

  38. Nelson PT, Smith CD, Abner EL, Wilfred BJ, Wang WX, Neltner JH, Baker M, Fardo DW, Kryscio RJ, Scheff SW, Jicha GA, Jellinger KA, Van Eldik LJ, Schmitt FA (2013) Hippocampal sclerosis of aging, a prevalent and high-morbidity brain disease. Acta Neuropathol 126:161–177

    Article  PubMed Central  PubMed  Google Scholar 

  39. Nisbet RM, Polanco JC, Ittner LM, Gotz J (2015) Tau aggregation and its interplay with amyloid-beta. Acta Neuropathol 129:207–220

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  40. Noda K, Sasaki K, Fujimi K, Wakisaka Y, Tanizaki Y, Wakugawa Y, Kiyohara Y, Iida M, Aizawa H, Iwaki T (2006) Quantitative analysis of neurofibrillary pathology in a general population to reappraise neuropathological criteria for senile dementia of the neurofibrillary tangle type (tangle-only dementia): the Hisayama Study. Neuropathology 26:508–518

    Article  PubMed  Google Scholar 

  41. Perl DP, Hof PR, Purohit DP, Loerzel AJ, Kakulas BA (2003) Hippocampal and entorhinal cortex neurofibrillary tangle formation in Guamanian Chamorros free of overt neurologic dysfunction. J Neuropathol Exp Neurol 62:381–388

    PubMed  Google Scholar 

  42. Rahimi J, Kovacs GG (2014) Prevalence of mixed pathologies in the aging brain. Alzheimers Res Ther 6:82

    Article  PubMed Central  PubMed  Google Scholar 

  43. Rijal Upadhaya A, Kosterin I, Kumar S, von Arnim CA, Yamaguchi H, Fandrich M, Walter J, Thal DR (2014) Biochemical stages of amyloid-beta peptide aggregation and accumulation in the human brain and their association with symptomatic and pathologically preclinical Alzheimer’s disease. Brain 137:887–903

    Article  PubMed  Google Scholar 

  44. Roe CM, Fagan AM, Grant EA, Hassenstab J, Moulder KL, Maue Dreyfus D, Sutphen CL, Benzinger TL, Mintun MA, Holtzman DM, Morris JC (2013) Amyloid imaging and CSF biomarkers in predicting cognitive impairment up to 7.5 years later. Neurology 80:1784–1791

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  45. Royall DR, Palmer RF (2014) The temporospatial evolution of neuritic plaque-related and independent tauopathies: implications for dementia staging. J Alzheimers Dis 40:541–549

    CAS  PubMed  Google Scholar 

  46. Santa-Maria I, Haggiagi A, Liu X, Wasserscheid J, Nelson PT, Dewar K, Clark LN, Crary JF (2012) The MAPT H1 haplotype is associated with tangle-predominant dementia. Acta Neuropathol 124:693–704

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  47. Singleton AB, Hall R, Ballard CG, Perry RH, Xuereb JH, Rubinsztein DC, Tysoe C, Matthews P, Cordell B, Kumar-Singh S, De Jonghe C, Cruts M, van Broeckhoven C, Morris CM (2000) Pathology of early-onset Alzheimer’s disease cases bearing the Thr113-114ins presenilin-1 mutation. Brain 123(Pt 12):2467–2474

    Article  PubMed  Google Scholar 

  48. Terry RD, Gonatas NK, Weiss M (1964) Ultrastructural studies in Alzheimer’s presenile dementia. Am J Pathol 44:269–297

    PubMed Central  CAS  PubMed  Google Scholar 

  49. Thal DR, Rub U, Orantes M, Braak H (2002) Phases of A beta-deposition in the human brain and its relevance for the development of AD. Neurology 58:1791–1800

    Article  PubMed  Google Scholar 

  50. Thal DR, von Arnim C, Griffin WS, Yamaguchi H, Mrak RE, Attems J, Upadhaya AR (2013) Pathology of clinical and preclinical Alzheimer’s disease. Eur Arch Psychiatry Clin Neurosci 263(Suppl 2):S137–S145

    Article  PubMed  Google Scholar 

  51. Thal DR, von Arnim CA, Griffin WS, Mrak RE, Walker L, Attems J, Arzberger T (2015) Frontotemporal lobar degeneration FTLD-tau: preclinical lesions, vascular, and Alzheimer-related co-pathologies. J Neural Transm. doi:10.1007/s00702-00014-01360-00706

  52. Toledo JB, Weiner MW, Wolk DA, Da X, Chen K, Arnold SE, Jagust W, Jack C, Reiman EM, Davatzikos C, Shaw LM, Trojanowski JQ (2014) Neuronal injury biomarkers and prognosis in ADNI subjects with normal cognition. Acta Neuropathol Commun 2:26

    Article  PubMed Central  PubMed  Google Scholar 

  53. van Harten AC, Smits LL, Teunissen CE, Visser PJ, Koene T, Blankenstein MA, Scheltens P, van der Flier WM (2013) Preclinical AD predicts decline in memory and executive functions in subjective complaints. Neurology 81:1409–1416

    Article  PubMed  Google Scholar 

  54. Vos SJ, Xiong C, Visser PJ, Jasielec MS, Hassenstab J, Grant EA, Cairns NJ, Morris JC, Holtzman DM, Fagan AM (2013) Preclinical Alzheimer’s disease and its outcome: a longitudinal cohort study. Lancet Neurol 12:957–965

    Article  PubMed Central  PubMed  Google Scholar 

  55. Yamada M (2003) Senile dementia of the neurofibrillary tangle type (tangle-only dementia): neuropathological criteria and clinical guidelines for diagnosis. Neuropathology 23:311–317

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kurt A. Jellinger.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jellinger, K.A., Alafuzoff, I., Attems, J. et al. PART, a distinct tauopathy, different from classical sporadic Alzheimer disease. Acta Neuropathol 129, 757–762 (2015). https://doi.org/10.1007/s00401-015-1407-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00401-015-1407-2

Keywords

Navigation