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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1046 Scopus citations

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 - Nov 14 2014

Keywords

  • Braak
  • Consensus
  • Neuropathology
  • TOD
  • TPSD

ASJC Scopus subject areas

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

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