Primary age-related tauopathy (PART): a common pathology associated with human aging

John F. Crary, John Q. Trojanowski, Julie A. Schneider, Jose F. Abisambra, Erin L. Abner, Irina Alafuzoff, Steven E. Arnold, Johannes Attems, Thomas G. Beach, Eileen H. Bigio, Nigel J. Cairns, Dennis W. Dickson, Marla Gearing, Lea T. Grinberg, Patrick R. Hof, Bradley T. Hyman, Kurt Jellinger, Gregory A. Jicha, Gabor G. Kovacs, David S. KnopmanJulia Kofler, Walter A. Kukull, Ian R. Mackenzie, Eliezer Masliah, Ann McKee, Thomas J. Montine, Melissa E. Murray, Janna H. Neltner, Ismael Santa-Maria, William W. Seeley, Alberto Serrano-Pozo, Michael L. Shelanski, Thor Stein, Masaki Takao, Dietmar R. Thal, Jonathan B. Toledo, Juan C. Troncoso, Jean Paul Vonsattel, Charles L. White, Thomas Wisniewski, Randall L. Woltjer, Masahito Yamada, Peter T. Nelson

Research output: Contribution to journalArticle

457 Citations (Scopus)

Abstract

We recommend a new term, “primary age-related tauopathy” (PART), to describe a pathology that is commonly observed in the brains of aged individuals. Many autopsy studies have reported brains with neurofibrillary tangles (NFTs) that are indistinguishable from those of Alzheimer’s disease (AD), in the absence of amyloid (Aβ) plaques. For these “NFT+/Aβ−” brains, for which formal criteria for AD neuropathologic changes are not met, the NFTs are mostly restricted to structures in the medial temporal lobe, basal forebrain, brainstem, and olfactory areas (bulb and cortex). Symptoms in persons with PART usually range from normal to amnestic cognitive changes, with only a minority exhibiting profound impairment. Because cognitive impairment is often mild, existing clinicopathologic designations, such as “tangle-only dementia” and “tangle-predominant senile dementia”, are imprecise and not appropriate for most subjects. PART is almost universally detectable at autopsy among elderly individuals, yet this pathological process cannot be specifically identified pre-mortem at the present time. Improved biomarkers and tau imaging may enable diagnosis of PART in clinical settings in the future. Indeed, recent studies have identified a common biomarker profile consisting of temporal lobe atrophy and tauopathy without evidence of Aβ accumulation. For both researchers and clinicians, a revised nomenclature will raise awareness of this extremely common pathologic change while providing a conceptual foundation for future studies. Prior reports that have elucidated features of the pathologic entity we refer to as PART are discussed, and working neuropathological diagnostic criteria are proposed.

Original languageEnglish (US)
Pages (from-to)755-766
Number of pages12
JournalActa Neuropathologica
Volume128
Issue number6
DOIs
StatePublished - 2014

Fingerprint

Tauopathies
Pathology
Neurofibrillary Tangles
Alzheimer Disease
Temporal Lobe
Autopsy
Brain
Biomarkers
Olfactory Bulb
Amyloid Plaques
Pathologic Processes
Terminology
Brain Stem
Atrophy
Dementia
Reference Values
Research Personnel

Keywords

  • Braak
  • Consensus
  • Neuropathology
  • TOD
  • TPSD

ASJC Scopus subject areas

  • Clinical Neurology
  • Pathology and Forensic Medicine
  • Cellular and Molecular Neuroscience

Cite this

Crary, J. F., Trojanowski, J. Q., Schneider, J. A., Abisambra, J. F., Abner, E. L., Alafuzoff, I., ... Nelson, P. T. (2014). Primary age-related tauopathy (PART): a common pathology associated with human aging. Acta Neuropathologica, 128(6), 755-766. https://doi.org/10.1007/s00401-014-1349-0

Primary age-related tauopathy (PART) : a common pathology associated with human aging. / Crary, John F.; Trojanowski, John Q.; Schneider, Julie A.; Abisambra, Jose F.; Abner, Erin L.; Alafuzoff, Irina; Arnold, Steven E.; Attems, Johannes; Beach, Thomas G.; Bigio, Eileen H.; Cairns, Nigel J.; Dickson, Dennis W.; Gearing, Marla; Grinberg, Lea T.; Hof, Patrick R.; Hyman, Bradley T.; Jellinger, Kurt; Jicha, Gregory A.; Kovacs, Gabor G.; Knopman, David S.; Kofler, Julia; Kukull, Walter A.; Mackenzie, Ian R.; Masliah, Eliezer; McKee, Ann; Montine, Thomas J.; Murray, Melissa E.; Neltner, Janna H.; Santa-Maria, Ismael; Seeley, William W.; Serrano-Pozo, Alberto; Shelanski, Michael L.; Stein, Thor; Takao, Masaki; Thal, Dietmar R.; Toledo, Jonathan B.; Troncoso, Juan C.; Vonsattel, Jean Paul; White, Charles L.; Wisniewski, Thomas; Woltjer, Randall L.; Yamada, Masahito; Nelson, Peter T.

In: Acta Neuropathologica, Vol. 128, No. 6, 2014, p. 755-766.

Research output: Contribution to journalArticle

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, Wisniewski, T, Woltjer, RL, Yamada, M & Nelson, PT 2014, 'Primary age-related tauopathy (PART): a common pathology associated with human aging', Acta Neuropathologica, vol. 128, no. 6, pp. 755-766. https://doi.org/10.1007/s00401-014-1349-0
Crary JF, Trojanowski JQ, Schneider JA, Abisambra JF, Abner EL, Alafuzoff I et al. Primary age-related tauopathy (PART): a common pathology associated with human aging. Acta Neuropathologica. 2014;128(6):755-766. https://doi.org/10.1007/s00401-014-1349-0
Crary, John F. ; Trojanowski, John Q. ; Schneider, Julie A. ; Abisambra, Jose F. ; Abner, Erin L. ; Alafuzoff, Irina ; Arnold, Steven E. ; Attems, Johannes ; Beach, Thomas G. ; Bigio, Eileen H. ; Cairns, Nigel J. ; Dickson, Dennis W. ; Gearing, Marla ; Grinberg, Lea T. ; Hof, Patrick R. ; Hyman, Bradley T. ; Jellinger, Kurt ; Jicha, Gregory A. ; Kovacs, Gabor G. ; Knopman, David S. ; Kofler, Julia ; Kukull, Walter A. ; Mackenzie, Ian R. ; Masliah, Eliezer ; McKee, Ann ; Montine, Thomas J. ; Murray, Melissa E. ; Neltner, Janna H. ; Santa-Maria, Ismael ; Seeley, William W. ; Serrano-Pozo, Alberto ; Shelanski, Michael L. ; Stein, Thor ; Takao, Masaki ; Thal, Dietmar R. ; Toledo, Jonathan B. ; Troncoso, Juan C. ; Vonsattel, Jean Paul ; White, Charles L. ; Wisniewski, Thomas ; Woltjer, Randall L. ; Yamada, Masahito ; Nelson, Peter T. / Primary age-related tauopathy (PART) : a common pathology associated with human aging. In: Acta Neuropathologica. 2014 ; Vol. 128, No. 6. pp. 755-766.
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abstract = "We recommend a new term, “primary age-related tauopathy” (PART), to describe a pathology that is commonly observed in the brains of aged individuals. Many autopsy studies have reported brains with neurofibrillary tangles (NFTs) that are indistinguishable from those of Alzheimer’s disease (AD), in the absence of amyloid (Aβ) plaques. For these “NFT+/Aβ−” brains, for which formal criteria for AD neuropathologic changes are not met, the NFTs are mostly restricted to structures in the medial temporal lobe, basal forebrain, brainstem, and olfactory areas (bulb and cortex). Symptoms in persons with PART usually range from normal to amnestic cognitive changes, with only a minority exhibiting profound impairment. Because cognitive impairment is often mild, existing clinicopathologic designations, such as “tangle-only dementia” and “tangle-predominant senile dementia”, are imprecise and not appropriate for most subjects. PART is almost universally detectable at autopsy among elderly individuals, yet this pathological process cannot be specifically identified pre-mortem at the present time. Improved biomarkers and tau imaging may enable diagnosis of PART in clinical settings in the future. Indeed, recent studies have identified a common biomarker profile consisting of temporal lobe atrophy and tauopathy without evidence of Aβ accumulation. For both researchers and clinicians, a revised nomenclature will raise awareness of this extremely common pathologic change while providing a conceptual foundation for future studies. Prior reports that have elucidated features of the pathologic entity we refer to as PART are discussed, and working neuropathological diagnostic criteria are proposed.",
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KW - Consensus

KW - Neuropathology

KW - TOD

KW - TPSD

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