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

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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Acknowledgments

We are extremely grateful to the patients, clinicians, and fellow researchers that made this effort possible. We also acknowledge the following funding sources: the Society for Supporting Research in Experimental Neurology, Vienna, Austria, National Institutes of Health Grants P50AG08702, R01 AG037212, P01AG07232, P30 AG028383, P50 AG005138, P50 AG016574, U01 AG006786, R01 AG041851, R01 AG011378, P30 AG028383, P50 AG016574, P01 AG003949, P30 AG012300, P50 AG005146, P50 AG005136, P50 AG025688, P50 AG005138, P01 AG002219, P50 AG005133, P50 AG005681, P01 AG003991, R01 AG038651, P30 AG019610, P30 AG013854, P30 AG036453, P30 AG010124, AG005131, AG184440, AG008051, Medical Research Council (MRC, G0400074), National Institute for Health Research (NIHR, R:CH/ML/0712), the Dunhill Medical Trust (R173/1110), Alzheimer’s Research UK (ARUK), and the Alzheimer’s Society (AS-PG-2013-011), Louis V. Gerstner, Jr., Foundation, Alzheimer’s Association (NIRG-11-204450), FP7 EU Project Develage (No. 278486), Comprehensive brain research network, Grant-in-Aid for Scientific Research (C; 26430060), and Daiwa Health Science Foundation, BrightFocus Foundation, Alzheimer’s Association NIRGD-12-242642, Alzheimer Forschung Initiative (AFI # 13803) (DRT); German Ministry for Research and Education (BMBF) FTLD-Net, Robert H. and Clarice Smith and Abigail Van Buren Alzheimer’s Disease Research Program of the Mayo Foundation.

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Crary, J.F., Trojanowski, J.Q., Schneider, J.A. et al. Primary age-related tauopathy (PART): a common pathology associated with human aging. Acta Neuropathol 128, 755–766 (2014). https://doi.org/10.1007/s00401-014-1349-0

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Keywords

  • TPSD
  • TOD
  • Braak
  • Neuropathology
  • Consensus