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

By John F. Crary, John Q. Trojanowski, Julie A. Schneider, J. Abisambra, E. Abner, I. Alafuzoff, S. Arnold, J. Attems, T. Beach, Eileen Bigio and 33 more. Acta Neuropathologica, 2014

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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.

Subfields: Neurology, Physiology, Psychiatry and Mental health

View Paper: https://www.semanticscholar.org/paper/20a007f11ad0e16a4a1783e687f7530620df864c

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Citations in the corpus

Alzheimer Disease: An Update on Pathobiology and Treatment Strategies (2019, neutral): “With age, tau pathology accumulates in the entorhinal cortex and medial temporal lobes, even in the absence of cognitive decline, as so called primary agerelated tauopathy (PART) (Crary et al., 2014).”
Comparison of multiple tau-PET measures as biomarkers in aging and Alzheimer's disease (2017, background): “The aggregation of hyperphosphorylated tau protein into intracellular neurofibrillary tangles (NFT) is one of the key pathological lesions in Alzheimer's disease (AD), but early tau pathology in medial temporal lobe regions is also common in cognitively normal elderly people (Crary et al., 2014).”
Alzheimer’s disease: experimental models and reality (2017, background): “A further complication is that there is extensive evidence showing medial temporal tauopathy predates Aβ deposition [15, 25, 35], presumably Fig.”
PET Imaging of Tau Deposition in the Aging Human Brain (2016, neutral): “Some pathologists have suggested that this may represent PART (Crary et al., 2014; Jellinger et al., 2015).”
Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020, background): “APOE4 significantly aggravated tau-mediated neurodegeneration in a tauopathy mouse model and induced tau aggregates in brain, while genetic ablation of APOE attenuated tau-induced neurodegeneration [469, 470].”
Reconsideration of Amyloid Hypothesis and Tau Hypothesis in Alzheimer's Disease (2018, background): “Furthermore, the brains of patients with primary age-related tauopathy (PART) contain NFTs that are indistinguishable from those of AD, in the absence of Aβ amyloid plaques (Crary et al., 2014; Duyckaerts et al., 2015; Jellinger et al., 2015).”
A/T/N: An unbiased descriptive classification scheme for Alzheimer disease biomarkers (2016, background): “For example, an A2T2N1 profile would be expected with pathologies such as ischemic cerebrovascular disease or hippocampal sclerosis whereas an A2T1N1 profile would be expected with PART (primary agerelated tauopathy).(44) An A1T2N1 profile might indicate an individual in the earliest stage of precli”
The neuropathological diagnosis of Alzheimer’s disease (2019, background): “The latter, when frequent, are associated with memory complaints observed in the elderly [130, 142].”
Revised criteria for diagnosis and staging of Alzheimer's disease: Alzheimer's Association Workgroup (2024, neutral): “5,42”
Pathology of Neurodegenerative Diseases. (2017, background): “This process is termed “primary age-related tauopathy” (PART), with most cases having early Braak NFT stages (I–IV) (Crary et al. 2014).”
The first NINDS/NIBIB consensus meeting to define neuropathological criteria for the diagnosis of chronic traumatic encephalopathy (2015, methodology): “The neuropathologists were given a tauopathy criteria guide that provided the provisional criteria for CTE [32] as well as published criteria for the other tauopathies (See supplementary material for full tauopathy criteria guide) [4, 7, 11, 21, 25, 34, 40, 47].”
Preclinical Alzheimer’s disease: Definition, natural history, and diagnostic criteria (2016, background): “These changes were recently designated as primary age-related tauopathy [31].”
Clinical diagnosis of Alzheimer’s disease: recommendations of the International Working Group (2021, background): “…elderly 101 *****. ___________________________________________________________________________ * Primary Age Related Tauopathy (PART) has emerged in the lexicon as an age-related normal occurrence of tauopathy in the absence or with a low extent of amyloid pathology (Thal ABeta Phase ≤ 2 102 ).”
Tau PET imaging in aging and early Alzheimer’s disease (2015, result): “Studies of (18)F T807 PET in younger subjects will be required to test whether entorhinal cortex binding in older normal subjects exceeds that in younger subjects, as predicted by reports with Braak staging, and whether this binding represents a tauopathy that, although primarily age-related, is acc”