PART (Primary age-related tauopathy)

Peter T Nelson MD PhD (Dr. Nelson of the University of Kentucky has no relevant financial relationships to disclose.)
Howard S Kirshner MD, editor. (Dr. Kirshner of Vanderbilt University School of Medicine has no relevant financial relationships to disclose.)
Originally released April 28, 2015; last updated January 09, 2020; expires January 09, 2023

This article includes discussion of PART (primary age-related tauopathy; previously described as tangle-predominant senile dementia or TPSD), tangle-only dementia, preferential development of neurofibrillary tangles without senile plaques, and senile dementia of the neurofibrillary tangle type (SD-NFT). The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations. To be clear, none of those “synonyms” are current, only PART is the current terminology for this brain disease.


Many autopsy studies have reported brains with neurofibrillary tangles that are indistinguishable from those of Alzheimer disease, in the absence of amyloid beta plaques. For these brains, the neurofibrillary tangles are mostly restricted to structures in the medial temporal lobe, and brainstem. Now biomarkers are also finding evidence of tauopathy in the absence of amyloid beta-type amyloidogenesis, and studies are confirming the brain changes are associated with cognitive impairment. This condition is termed “primary age related tauopathy” or PART. Symptoms in persons with PART usually range from normal to amnestic cognitive changes, with only a minority exhibiting profound impairment (unless additional comorbid pathologies are present, which is not unusual). PART is almost universally detectable at autopsy among elderly individuals who lack amyloid beta plaques; in advanced old age, approximately 25% of persons lack amyloid beta plaques.

As a rule, every person past 80 years of age (and the great majority over 50 years of age) has some PART pathology--it is presumed to exist even in those with Alzheimer disease wherein the plaque or tangle pathology renders impossible the independent evaluation of the PART pathology. Those lacking amyloid plaques, but with more severe PART pathology (Braak stage III/IV), are more likely to have lower MMSE scores and subjective memory complaints or MCI. If there are other pathologies and/or if the PART pathology is severe, it can contribute to MCI or full-blown dementia. The clinical-pathological correlation studies indicate the challenge of defining a “disease” versus “normal” state in advanced old age, and PART helps explain why the average (“normal”) and even above-average neurocognitive scores among nondemented persons becomes lower in advanced old age.

New data have emerged in 2 different areas related to PART: biomarkers and clinical-pathological correlations, and these are discussed below.

There also has been some debate in the field about this pathologic entity (Duyckaerts et al 2015), although some degree of acceptance is widespread with more than 600 citations of the original paper from 2014-2019.

Key points


• PART is a pathologically defined entity that helps explain normative loss in cognitive function in advanced old age.


• Genetic contributors to PART do not include APOE (unlike Alzheimer disease).


• Clinical-pathological correlations indicate that PART usually has a more moderate outcome, ie, a less devastating clinical course, than Alzheimer disease.


• PART features tauopathy in medial temporal lobe and brainstem, resembling Alzheimer disease, but, by definition, there are no amyloid plaques.


• PART may be obscured by other pathologies, particularly Alzheimer disease.


• PART is ubiquitous among the non-Alzheimer disease elderly, but there is variation in severity between individuals.

Historical note and terminology

PART was described in 2014 (Crary et al 2014); however, patients with mild-to-moderate Alzheimer disease-type neurofibrillary degeneration in the medial temporal lobe, but lacking amyloid beta plaques, have been described in European, Japanese, and North and South American cohorts (Schnitzler 1911; Goodman 1953; Hauw et al 1986; Ulrich et al 1992; Ikeda et al 1993; Bancher and Jellinger 1994; Giannakopoulos et al 1994; Yamada et al 1996; Yamada et al 2001; Itoh et al 1996; Jellinger and Bancher 1998; Yamada 2003; Jellinger and Attems 2007).

Prior terminology included “tangle-predominant senile dementia,” “tangle-only dementia,” “preferential development of neurofibrillary tangles without senile plaques,” and “senile dementia of the neurofibrillary tangle type” (SD-NFT), among other names (Hof et al 1992; Ulrich et al 1992; Mizutani et al 1993; Bancher and Jellinger 1994; Bouras et al 1994; Itoh et al 1996; Ikeda et al 1999; Dickson et al 2011).

PART pathology appears to correlate with a biomarker profile that has been termed “SNAP,” or “suspected nonamyloid pathology/pathophysiology” (Jack et al 2012; Knopman et al 2013; Vos et al 2013; Jack 2014). However, there are other non-Alzheimer diseases that contribute to SNAP, and for a patient with profound cognitive impairments, PART would probably not be the only underlying disease.

Studies have helped underscore differences between Alzheimer disease and PART (Besser et al 2017; Bell et al 2019), including the relatively benign clinical features of PART in comparison to Alzheimer disease.

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