PART (primary age-related tauopathy) …

Peter T Nelson MD PhD

Neurobehavioral & Cognitive Disorders

Updated 11.17.2025
Released 04.28.2015
Expires For CME 11.17.2028

PART (Primary age-related tauopathy)

Author: Peter T Nelson MD PhD

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Editor: Howard S Kirshner MD

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PART (Primary age-related tauopathy)

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Introduction

Overview

Alzheimer disease is the most common underlying condition for dementia and, pathologically, Alzheimer disease is characterized by amyloid plaques and neurofibrillary tangles by definition. 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. Clinical biomarkers are also finding evidence of tauopathy in the absence of amyloid beta-type amyloidogenesis, and associated 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 people lack amyloid beta plaques.

As a rule, every person past 80 years of age (and the great majority over 50 years of age) (25) 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 NFT stages III or IV), are more likely to have lower MMSE scores and subjective memory complaints or mild cognitive impairment. If there are other pathologies or if the PART pathology is severe, it can contribute to mild cognitive impairment 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 two different areas related to PART: biomarkers and clinical-pathological correlations. There has also been some debate in the field about this pathologic entity (19; 12), although some degree of acceptance is widespread, with more than 1500 citations of the original paper from 2014 to 2025. For an overall review, see (60).

Key points

	• PART is a pathologically defined entity that helps explain normative loss in cognitive function in advanced old age, even in people lacking neuropathologic changes due to Alzheimer disease, ie, beta-amyloid plaques.
	• 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 (as soon as early 20s), but there is variation in severity between individuals.

Historical note and terminology

PART was described in 2014 (15); however, patients with mild-to-moderate Alzheimer disease-type neurofibrillary degeneration in the medial temporal lobe, but lacking amyloid beta plaques, were previously described in European, Japanese, and North and South American cohorts (72; 03; 29; 35).

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 (24; 72; 48; 03; 08; 29; 27; 17).

PART pathology appears to correlate with a clinical biomarker profile that has been termed “SNAP,” or “suspected nonamyloid pathology/pathophysiology,” describing persons with possible age-related neurodegeneration but lacking Alzheimer disease-type A-beta amyloidogenesis according to biomarkers (32; 40; 73; 30). 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 (06; 05), including the relatively benign clinical features of PART in comparison to Alzheimer disease.

Clinical manifestations

Presentation and course

Severe PART can be associated with cognitive impairment according to studies that interpret cases shown to lack amyloid beta pathology but before PART was described formally (27; 51). However, various confounders, including the high prevalence of comorbid brain (and non-CNS) diseases in the “oldest-old,” make clinicopathological correlations challenging in this population (55; 53; 36; 62; 02). Most relevant prior studies have either focused on the most severe cases (with what was termed “tangle-only dementia” or some similar nomenclature) or have investigated the associations between other tauopathic subtypes (22; 35; 70).

The average age of death in individuals with PART is generally higher than in those with “pure” Alzheimer disease pathology (35; 51; 16; 15). Whereas cognitively impaired subjects with PART often carry a clinical diagnosis of possible or probable Alzheimer disease (59), the coexistence of PART and Alzheimer disease in aging is an inevitable complicating factor (81). Analyses of the National Alzheimer’s Coordinating Center (NACC) autopsy database found that approximately 14% of subjects clinically diagnosed with mild-to-moderate probable Alzheimer disease had no or sparse neuritic plaques (04; 65; 06). Data presented by Crary and colleagues indicated the following: the pathology is common and Braak stage “0” (no tangles) is unusual in older individuals; there is no strong association between PART and APOE genotype; and the more severe PART pathology is associated with a higher age of death and lower scores on cognitive tests (15). The relatively rare APOE e2 allele has been found to be more common in people with PART (61).

Since the original article that presented PART as a clinical-pathological entity and that provided analyses of data indicating direct evidence of an impact by the disease on cognition (15), there have been developments, particularly in two areas: (1) additional clinical-pathological correlation studies and (2) clinical studies to highlight the importance and relevance of PART in dementia-related clinical biomarkers.

Clinical-pathology studies published since 2015 indicate that PART plays a role in dementia as well as mild cognitive impairment and subjective memory complaints (01; 41; 34; 37; 06; 05). Unfortunately, the awareness of PART by clinicians is relatively low, which is unfortunate because the clinical course of the disease is not identical to Alzheimer disease, with which it may be diagnostically conflated (07; 69). The relevance of the pathology to states of cognitive impairment is influenced by a number of factors that include the severity of the PART pathology as well as the presence and severity of comorbid pathologies (many of which, including Alzheimer disease, cerebrovascular disease, and alpha-synucleinopathy, are very common in the older population). In one study, it was found that in PART, independent predictors of symptomatic status included depression (adjusted odds ratio [aOR] 4.20), Braak stage (aOR 1.42), and history of stroke (aOR 8.09) (06). A study of confirmed PART cases with retrospective MRI showed that “PART is associated with medial temporal lobe atrophy and predominantly affects semantic memory/language” (58). More work is required in this area. A study confirmed prior work indicating that the cognitive impairment of PART is less severe than Alzheimer disease (71). Tau-PET scans confirm the association between increased PART and cognitive impairments (14; 21).

A study using the large National Alzheimer’s Coordinating Center (NACC) data set (n=2884) showed that “…PART subjects had selective deficits in measures of processing speed, executive function, and visuospatial function” (74). Another paper analyzing digital pathology via artificial intelligence methods highlighted again that the severity of PART is associated with cognitive impairment (46).

A key question with regard to PART is the biomarker profile. An excellent discussion of this consideration can be found in a 2014 article (30), which elaborates the argument that patients with PART pathology probably have a biomarker profile termed “SNAP,” or “suspected non-amyloid pathology” (32; 40; 73; 30), where some evidence of neuronal injury or tau protein pathology is identified by CSF or neuroimaging methods, but there is no evidence of amyloid beta decrease in CSF or a plaque-amyloid ligand augmentation on PET imaging. Data from additional studies support a biomarker fingerprint of PART (31; 33; 44; 67), but the analyses require refinement because subsequent studies underscore that PART often is present in a prodromal form (in cognitively unimpaired persons) (18). Unfortunately, there is no consensus-based system for diagnostically staging the disease in the clinical context. Additional discussion of the utility of tau biomarkers for PART detection in the clinical context is presented in the following sections.

Prognosis and complications

Prognosis of PART in isolation (without comorbid pathologies) is usually relatively benign in comparison to almost all other dementia-related conditions (05). PART can play an important role in the very common scenario of worsening an already complex mixture of brain pathologies (Lewy body disease, TDP-43 proteinopathy, cerebrovascular pathologies, etc.). It is important to emphasize that this scenario is extremely common, occurring in approximately 50% of people that escape the sequelae of Alzheimer-type plaques and tangles (the reported proportion is dependent on how one operationalizes each disease subtype).

Clinical vignette

An 80-year-old, highly educated individual was followed as a research volunteer at an Alzheimer Disease Research Center. On presentation, he met no criteria for clinical cognitive impairment and was followed as a "normal" subject. However, in his third year of longitudinal follow-up, he described "slippage" in short-term memory and was diagnosed clinically with mild cognitive impairment. An MRI at 83 years of age showed mild-to-moderate medial temporal lobe atrophy. He was followed longitudinally until his death at age 91. Although he suffered from mild cognitive impairment, a diagnosis supported by objective neurocognitive testing, he was still able to teach a class well into his 80s and maintained his ability to perform activities of daily living. His clinical course was complicated by severe rheumatoid arthritis and lung cancer, and he died from lung cancer with dementia never diagnosed.

Mild cognitive impairment in elderly man

The subject was followed for 11 years from normal status until death at 91 years of age. Results of longitudinal neurocognitive tests are shown (a), including the Mini-Mental State Examination (MMSE) for global cognitive function ...

Biological basis

Etiology and pathogenesis

Etiology and pathogenesis are not currently understood.

Pathologic manifestations. The grading system that applies to PART is Braak neurofibrillary staging (10). The pathologic continuum of PART includes pretangle or cortical pretangle (up to Stage Ib), entorhinal (I-II), or limbic (III-IV) Braak stages (10; 11; 09). The neurofibrillary changes in PART resemble (or are identical to) those in early (but not “high level of pathology”) Alzheimer disease brains. Immunohistochemical and biochemical studies have found that neurofibrillary tangles in PART, as in Alzheimer disease, contain accumulation of both 3-repeat and 4-repeat tau isoforms (28; 66; 35; 64). In Alzheimer disease, electron microscopy demonstrates paired helical filaments, which are considered a disease hallmark (39; 78; 63). The tau fibrils in brains with PART pathology also display a typical paired helical filament morphology (29; 26; 64; 15). Pathologically, PART neurofibrillary tangles preferentially affect the CA2 portion of the hippocampus (75). Formal pathological diagnostic criteria are provided by Crary and colleagues (15).

It has been noted that there is possibly some overlap between PART and chronic traumatic encephalopathy (CTE) as both are tauopathies with both 3R and 4R tau and, thus, PART may, in some cases, be exacerbated by chronic traumatic factors such as sports injuries (47).

PART is defined as lacking Abeta plaques. As a rule, every person gets some tangles by middle age, so just about any person lacking plaques (approximately 25% of those over 80 years of age lack Abeta plaques) has PART. The key point is that some people have more severe PART than others, ie, more dense and widespread tau pathology in the medial temporal lobes. The question is what occurs in these people with more severe PART pathology. A study showed that in parallel with higher Braak neurofibrillary tangle stages (PART pathology tops out at Braak neurofibrillary tangle stage IV for unknown reasons), hippocampal synaptic changes become conspicuous (49).

It is important to recognize that PART occurs predominantly in the context of the aged brain that usually shows a complex mixture of neuropathologic lesions. There may be interactions between those lesions, including PART; more specifically, TDP-43 proteinopathy has been shown to affect the pathologic phenotype of tau or tangle proteinopathy in PART (68). This is important because TDP-43 proteinopathy is another common (approximately 25% of elderly) non-Alzheimer disease of brain aging with strong impact on cognition; TDP-43 proteinopathy exerts stronger impact (in isolation) than PART but less strong than Alzheimer disease in community autopsy cohorts (52; 50). It has been shown that PART pathology is more severe (higher Braak NFT stages) in cases with comorbid TDP-43 pathology (54). A large (n=1589 cases) autopsy study from Japan underscored that PART is often comorbid with other pathologies, including argyrophilic grains (80).

Differential diagnosis

A key issue pertinent to differential diagnosis is the biomarker profile. Patients with PART pathology probably have a biomarker profile that has been termed “SNAP,” or “suspected non-amyloid pathology” (32; 40; 73; 30), where some evidence of neuronal injury or tau protein pathology is identified by CSF or neuroimaging methods, but there is no evidence of amyloid beta decrease in CSF or a plaque-amyloid ligand augmentation on PET imaging. Another possible aid in differential diagnosis is that the cognitive trajectory (impairment over time) may be more mild in PART than full-blown Alzheimer disease. Please see discussion above about the importance of prevalent comorbid pathologies in terms of the impacts on cognition and behavior. The increasing clinical relevance of imaging and biofluid-based biomarkers are discussed in the Diagnostic workup section.

Confusing conditions

• Alzheimer disease
• Vascular cognitive impairment
• Limbic-predominant age-related TDP-43 proteinopathy (LATE)
• Age-related tau astrogliopathy (ARTAG)

There has been appreciation of the complexity of non-Alzheimer pathologies that affect the medial temporal lobe. In addition to PART, another common pathology linked to brain aging is limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC). Briefly, LATE-NC is characterized by TDP-43 proteinopathy that preferably affects the amygdala and hippocampus. LATE-NC is seen in approximately one third of brains beyond the age of 85 and has a strong impact on cognition. Notably, persons with LATE-NC are relatively likely to have more severe (higher Braak NFT stage) PART (54).

Associated or underlying disorders

It is presently possible to assess the risk of Alzheimer disease (CSF and PET scans for A-beta amyloidosis) and large-vessel vascular pathologies. However, small-vessel pathologies, LATE, and ARTAG still await specific clinical biomarkers for making confident differential diagnoses in the clinical context.

Diagnostic workup

There is no current consensus-based diagnostic workup for PART. However, this diagnosis should certainly be in the differential for individuals with a biomarker profile that suggests tauopathy in the absence of amyloid beta amyloidogenesis detected with PET or CSF profiling (it is hoped that a blood-based diagnostic test will be available in the future). For most people with this profile, the short-term outcomes would be better than those with true Alzheimer disease-type biomarker profile that includes amyloid beta amyloidogenesis. However, the common comorbid pathologies (eg, large and small vessel cerebrovascular diseases and alpha-synucleinopathies) may still exert strong deleterious impact on cognition independent of PART pathology (45). A biomarker study concluded that the pathology of PART “might not be as benign as commonly thought” (21). Numerous biomarker studies have shown evidence of PART in live patients (33; 57), but there are presently no consensus-based recommendations for diagnostically staging the disease in the clinical context. Importantly, because nearly all adults that lack Abeta plaques have some PART, the question is not the presence or absence of the condition but the severity of the PART pathology. High-pathology PART (Braak neurofibrillary tangle stage IV) would be much more likely to exert clinical impact than low-pathology PART (Braak neurofibrillary tangle stages 0/I). In any case, studies have intensively queried Alzheimer-related biomarkers (by PET and biofluid studies) as amyloid beta-oriented immunotherapy clinical management has shed new light on PART biomarkers.

Three findings related to biomarkers in PART are highlighted here (38):

(1) Flortaucipir PET has limited ability to detect PART, and imaging-defined PART did not correspond with pathologically defined PART.

(2) A-T+ (presumably mostly PART) cases could be identified using plasma pTau-181.

(3) Plasma tau markers show unexpectedly high variability, even in normal healthy controls.

Studies have again underscored that the tau pathology of PART may be difficult to discern using tau biomarkers; in other words, the less-severe tauopathy of PART may not be detected, whereas the more-severe tauopathy of Alzheimer neuropathologic changes can be detected (43; 42; 20).

References

01: Abner EL, Kryscio RJ, Schmitt FA, et al. Outcomes after diagnosis of mild cognitive impairment in a large autopsy series. Ann Neurol 2017;81(4):549-59. PMID 28224671
02: Agrawal S, Yu L, Barnes LL, et al. Cognitive decline in community-dwelling older persons with primary age-related tauopathy: role of anatomical location of tangles and other co-existing brain pathologies. Acta Neuropathol 2025;150(1):8. PMID 40705123
03: Bancher C, Jellinger KA. Neurofibrillary tangle predominant form of senile dementia of Alzheimer type: a rare subtype in very old subjects. Acta Neuropathol 1994;88(6):565-70. PMID 7879604
04: Beekly DL, Ramos EM, Lee WW, et al. The National Alzheimer's Coordinating Center (NACC) database: the Uniform Data Set. Alzheimer Dis Assoc Disord 2007;21(3):249-58. PMID 17804958
05: Bell WR, An Y, Kageyama Y, et al. Neuropathologic, genetic, and longitudinal cognitive profiles in primary age-related tauopathy (PART) and Alzheimer's disease. Alzheimers Dement 2019;15(1):8-16. PMID 30465754
06: Besser LM, Crary JF, Mock C, Kukull WA. Comparison of symptomatic and asymptomatic persons with primary age-related tauopathy. Neurology 2017;89(16):1707-15. PMID 28916532
07: Besser LM, Mock C, Teylan MA, Hassenstab J, Kukull WA, Crary JF. Differences in cognitive impairment in primary age-related tauopathy versus Alzheimer disease. J Neuropathol Exp Neurol 2019;78(3):219-28. PMID 30715383
08: Bouras C, Hof PR, Giannakopoulos P, Michel JP, Morrison JH. Regional distribution of neurofibrillary tangles and senile plaques in the cerebral cortex of elderly patients: a quantitative evaluation of a one-year autopsy population from a geriatric hospital. Cereb Cortex 1994;4(2):138-50. PMID 8038565
09: Braak H, Alafuzoff I, Arzberger T, Kretzschmar H, Del Tredici K. Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry. Acta Neuropathol 2006;112(4):389-404. PMID 16906426
10: Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 1991;82(4):239-59. PMID 1759558
11: Braak H, Braak E, Bohl J. Staging of Alzheimer-related cortical destruction. Eur Neurol 1993;33(6):403-8. PMID 8307060
12: Braak H, Mayer B, Feldengut S, Schon M, Del Tredici K. Sequence and trajectory of early Alzheimer's disease-related tau inclusions in the hippocampal formation of cases without amyloid-beta deposits. Acta Neuropathol 2025;149(1):50. PMID 40407905
13: Braak H, Thal DR, Ghebremedhin E, Del Tredici K. Stages of the pathologic process in Alzheimer disease: age categories from 1 to 100 years. J Neuropathol Exp Neurol 2011;70(11):960-9. PMID 22002422
14: Chen X, Cassady KE, Adams JN, Harrison TM, Baker SL, Jagust WJ. Regional tau effects on prospective cognitive change in cognitively normal older adults. J Neurosci 2021;41(2):366-75. PMID 33219003
15: Crary JF, Trojanowski JQ, Schneider JA, et al. Primary age-related tauopathy (PART): a common pathology associated with human aging. Acta Neuropathol 2014;128(6):755-66.** PMID 25348064
16: Dawe RJ, Bennett DA, Schneider JA, Arfanakis K. Neuropathologic correlates of hippocampal atrophy in the elderly: a clinical, pathologic, postmortem MRI study. PLoS One 2011;6(10):e26286. PMID 22043314
17: Dickson DW, Kouri N, Murray ME, Josephs KA. Neuropathology of Frontotemporal Lobar Degeneration-Tau (FTLD-Tau). J Mol Neurosci 2011;45(3):384-9. PMID 21720721
18: Donohue MC, Sperling RA, Petersen R, et al. Association between elevated brain amyloid and subsequent cognitive decline among cognitively normal persons. JAMA 2017;317(22):2305-16. PMID 28609533
19: Duyckaerts C, Braak H, Brion JP, et al. PART is part of Alzheimer disease. Acta Neuropathol 2015;129(5):749-56. PMID 25628035
20: Gerard T, Colmant L, Malotaux V, et al. Tau PET imaging with [(18)F]MK-6240: limited affinity for primary tauopathies and high specificity for Alzheimer's disease. Eur J Neurol 2025;32(2):e70068. PMID 39957301
21: Groot C, Doré V, Robertson J, et al. Mesial temporal tau is related to worse cognitive performance and greater neocortical tau load in amyloid-β-negative cognitively normal individuals. Neurobiol Aging 2021;97:41-8. PMID 33130455
22: Grudzien A, Shaw P, Weintraub S, Bigio E, Mash DC, Mesulam MM. Locus coeruleus neurofibrillary degeneration in aging, mild cognitive impairment and early Alzheimer's disease. Neurobiol Aging 2007;28(3):327-35. PMID 16574280
23: Harris GA, Hirschfeld LR, Gonzalez MI, Pritchard MC, May PC. Revisiting the therapeutic landscape of tauopathies: assessing the current pipeline and clinical trials. Alzheimers Res Ther 2025;17(1):129. PMID 40462159
24: Hof PR, Bouras C, Buée L, Delacourte A, Perl DP, Morrison JH. Differential distribution of neurofibrillary tangles in the cerebral cortex of dementia pugilistica and Alzheimer's disease cases. Acta Neuropathol. 1992;85(1):23-30. PMID 1285493
25: Humphrey WO, Martindale R, Pendlebury WW, DeWitt JC. Primary age-related tauopathy (PART) in the general autopsy setting: not just a disease of the elderly. Brain Pathol 2021;31(2):381-4. PMID 33147361
26: Ikeda K, Akiyama H, Arai T, et al. A subset of senile dementia with high incidence of the apolipoprotein E epsilon2 allele. Ann Neurol 1997;41(5):693-5. PMID 9153535
27: Ikeda K, Akiyama H, Arai T, et al. Clinical aspects of 'senile dementia of the tangle type'-- a subset of dementia in the senium separable from late-onset Alzheimer's disease. Dement Geriatr Cogn Disord 1999;10(1):6-11. PMID 9844032
28: Iseki E, Tsunoda S, Suzuki K, et al. Regional quantitative analysis of NFT in brains of non-demented elderly persons: comparisons with findings in brains of late-onset Alzheimer's disease and limbic NFT dementia. Neuropathology 2002;22(1):34-9. PMID 12030413
29: Itoh, Yamada M, Yoshida R, et al. Dementia characterized by abundant neurofibrillary tangles and scarce senile plaques: a quantitative pathological study. Eur Neurol 1996;36(2):94-7. PMID 8654493
30: Jack CR Jr. PART and SNAP. Acta Neuropathol 2014;128(6):773-6. PMID 25380757
31: Jack CR Jr, Bennett DA, Blennow K, et al. A/T/N: An unbiased descriptive classification scheme for Alzheimer disease biomarkers. Neurology 2016;87(5):539-47. PMID 27371494
32: Jack CR Jr, Knopman DS, Weigand SD, et al. An operational approach to National Institute on Aging-Alzheimer's Association criteria for preclinical Alzheimer disease. Ann Neurol 2012;71(6):765-75. PMID 22488240
33: Jack CR Jr, Wiste HJ, Weigand SD, et al. Age-specific and sex-specific prevalence of cerebral β-amyloidosis, tauopathy, and neurodegeneration in cognitively unimpaired individuals aged 50-95 years: a cross-sectional study. Lancet Neurol 2017;16(6):435-444. PMID 28456479
34: Jefferson-George KS, Wolk DA, Lee EB, McMillan CT. Cognitive decline associated with pathological burden in primary age-related tauopathy. Alzheimers Dement 2017;13(9):1048-53. PMID 28322204
35: Jellinger KA, Attems J. Neurofibrillary tangle-predominant dementia: comparison with classical Alzheimer disease. Acta Neuropathol 2007;113(2):107-17. PMID 17089134
36: Jellinger KA, Attems J. Prevalence and pathology of vascular dementia in the oldest-old. J Alzheimers Dis 2010;21(4):1283-93. PMID 21504129
37: Josephs KA, Murray ME, Tosakulwong N, et al. Tau aggregation influences cognition and hippocampal atrophy in the absence of beta-amyloid: a clinico-imaging-pathological study of primary age-related tauopathy (PART). Acta Neuropathol 2017;133(5):705-15. PMID 28160067
38: Josephs KA, Tosakulwong N, Weigand SD, et al. Flortaucipir PET uncovers relationships between tau and amyloid-beta in primary age-related tauopathy and Alzheimer's disease. Sci Transl Med 2024;16(757):eado8076. PMID 39047115
39: Kidd M. Paired helical filaments in electron microscopy of Alzheimer's disease. Nature 1963;197:192-3. PMID 14032480
40: Knopman DS, Jack CR Jr, Wiste HJ, et al. Brain injury biomarkers are not dependent on beta-amyloid in normal elderly. Ann Neurol 2013;73(4):472-80. PMID 23424032
41: Kryscio RJ, Abner EL, Jicha GA, et al. Self-reported memory complaints: a comparison of demented and unimpaired outcomes. J Prev Alzheimers Dis 2016;3(1):13-9. PMID 27019842
42: Lavrova A, Pham NTT, Vernon CJ, et al. (18)F-FDG PET in detection of primary age-related tauopathy (PART) - is there a role? Insights from an imaging-pathology correlation study. Alzheimers Dement 2025;21(8):e70568. PMID 40827317
43: Lavrova A, Satoh R, Pham NTT, et al. Investigating the feasibility of (18)F-flortaucipir PET imaging in the antemortem diagnosis of primary age-related tauopathy (PART): an observational imaging-pathological study. Alzheimers Dement 2024;20(12):8605–14. PMID 39417408
44: Lowe VJ, Curran G, Fang P, et al. An autoradiographic evaluation of AV-1451 Tau PET in dementia. Acta Neuropathol Commun 2016;4(1):58. PMID 27296779
45: Martinez N, Bharani KL, Hasan S, Hayes CA. Micro infarcts are associated with cognitive impairment in neurofibrillary tangle predominant decedents: evidence from the NACC autopsy cohort. Alzheimers Res Ther 2025;17(1):216. PMID 41035071
46: Marx GA, Koenigsberg DG, McKenzie AT, et al. Artificial intelligence-derived neurofibrillary tangle burden is associated with antemortem cognitive impairment. Acta Neuropathol Commun 2022;10(1):157. PMID 36316708
47: McKee AC, Cairns NJ, Dickson DW, et al. The first NINDS/NIBIB consensus meeting to define neuropathological criteria for the diagnosis of chronic traumatic encephalopathy. Acta Neuropathol 2016;131(1):75-86. PMID 26667418
48: Mizutani T, Kasahara M, Yamada S, Mukai M, Amano N. [Study on the neuropathological diagnosis of senile dementia of the Alzheimer type]. [Japanese]. No To Shinkei. 1993 Apr;45(4):333-42. PMID 8334018
49: Morris M, Coste GI, Redding-Ochoa J, et al. Hippocampal synaptic alterations associated with tau pathology in primary age-related tauopathy. J Neuropathol Exp Neurol 2023;82(10):836-44. PMID 37595576
50: Nag S, Yu L, Wilson RS, Chen EY, Bennett DA, Schneider JA. TDP-43 pathology and memory impairment in elders without pathologic diagnoses of AD or FTLD. Neurology 2017;88(7):653-60. PMID 28087828
51: Nelson PT, Abner EL, Schmitt FA. Brains with medial temporal lobe neurofibrillary tangles but no neuritic amyloid plaques are a diagnostic dilemma but may have pathogenetic aspects distinct from Alzheimer disease. J Neuropathol Exp Neurol 2009;68(7):774-84. PMID 19535994
52: Nelson PT, Abner EL, Schmitt FA, et al. Modeling the association between 43 different clinical and pathological variables and the severity of cognitive impairment in a large autopsy cohort of elderly persons. Brain Pathol 2010;20(1):66-79. PMID 19021630
53: Nelson PT, Alafuzoff I, Bigio EH, et al. Correlation of Alzheimer disease neuropathologic changes with cognitive status: a review of the literature. J Neuropathol Exp Neurol 2012;71(5):362-81. PMID 22487856
54: Nelson PT, Brayne C, Flanagan ME, et al. Frequency of LATE neuropathologic change across the spectrum of Alzheimer’s disease neuropathology: combined data from 13 community-based or population-based autopsy cohorts. Acta Neuropathol 2022;144(1):27-44. PMID 35697880
55: Nelson PT, Jicha GA, Schmitt FA, et al. Clinicopathologic correlations in a large Alzheimer disease center autopsy cohort: neuritic plaques and neurofibrillary tangles do count when staging disease severity. J Neuropathol Exp Neurol 2007;66(12):1136-46. PMID 18090922
56: Neltner JH, Abner EL, Jicha GA, et al. Brain pathologies in extreme old age. Neurobiol Aging 2016;37:1-11. PMID 26597697
57: Phillips JS, Das SR, McMillan CT, et al. Tau PET imaging predicts cognition in atypical variants of Alzheimer's disease. Hum Brain Mapp 2018;39(2):691-708. PMID 29105977
58: Quintas-Neves M, Teylan MA, Besser L, et al. Magnetic resonance imaging brain atrophy assessment in primary age-related tauopathy (PART). Acta Neuropathol Commun 2019;7(1):204. PMID 31818331
59: Ranginwala NA, Hynan LS, Weiner MF, White CL 3rd. Clinical criteria for the diagnosis of Alzheimer disease: still good after all these years. Am J Geriatr Psychiatry 2008;16(5):384-8. PMID 18448850
60: Richardson TE, Walker JM, Farrell K, Oliveira TG, White CL 3rd, Crary JF. Primary age-related tauopathy. Acta Neuropathol 2025;150(1):40.** PMID 41065841
61: Robinson AC, Davidson YS, Roncaroli F, et al. Influence of APOE genotype in primary age-related tauopathy. Acta Neuropathol Commun 2020;8(1):215. PMID 33287896
62: Robinson JL, Geser F, Corrada MM, et al. Neocortical and hippocampal amyloid-beta and tau measures associate with dementia in the oldest-old. Brain 2011;134(Pt 12):3708-15. PMID 22120149
63: Ruben GC, Wang JZ, Iqbal K, Grundke-Iqbal I. Paired helical filaments (PHFs) are a family of single filament structures with a common helical turn period: negatively stained PHF imaged by TEM and measured before and after sonication, deglycosylation, and dephosphorylation. Microsc Res Tech 2005;67(3-4):175-95. PMID 16104003
64: Santa-Maria I, Haggiagi A, Liu X, et al. The MAPT H1 haplotype is associated with tangle-predominant dementia. Acta Neuropathol 2012;124(5):693-704. PMID 22802095
65: Serrano-Pozo A, Qian J, Monsell SE, et al. Mild to moderate Alzheimer dementia with insufficient neuropathological changes. Ann Neurol 2014;75(4):597-601. PMID 24585367
66: Shiarli AM, Jennings R, Shi J, et al. Comparison of extent of tau pathology in patients with frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17), frontotemporal lobar degeneration with Pick bodies and early onset Alzheimer's disease. Neuropathol Appl Neurobiol 2006;32(4):374-87. PMID 16866983
67: Shimada H, Kitamura S, Shinotoh H, et al. Association between Aβ and tau accumulations and their influence on clinical features in aging and Alzheimer's disease spectrum brains: A [11C]PBB3-PET study. Alzheimers Dement (Amst) 2016;6:11-20. PMID 28138509
68: Smith VD, Bachstetter AD, Ighodaro E, et al. Overlapping but distinct TDP-43 and tau pathologic patterns in aged hippocampi. Brain Pathol 2018;28(2):264-73. PMID 28281308
69: Teylan M, Besser LM, Crary JF, et al. Clinical diagnoses among individuals with primary age-related tauopathy versus Alzheimer’s neuropathology. Lab Invest 2019;99(7):1049-55. PMID 30710118
70: Takahashi J, Shibata T, Sasaki M, et al. Detection of changes in the locus coeruleus in patients with mild cognitive impairment and Alzheimer's disease: high-resolution fast spin-echo T1-weighted imaging. Geriatr Gerontol Int 2015;15(3):334-40. PMID 24661561
71: Teylan M, Mock C, Gauthreaux K, et al. Cognitive trajectory in mild cognitive impairment due to primary age-related tauopathy. Brain 2020;143(2):611-21. PMID 31942622
72: Ulrich J, Spillantini MG, Goedert M, Dukas L, Staehelin HB. Abundant neurofibrillary tangles without senile plaques in a subset of patients with senile dementia. Neurodegeneration 1992;257-84.
73: Vos SJ, Xiong C, Visser PJ, et al. Preclinical Alzheimer's disease and its outcome: a longitudinal cohort study. Lancet Neurol 2013;12(10):957-65. PMID 24012374
74: Walker JM, Gonzales MM, Goette W, et al. Cognitive and neuropsychological profiles in Alzheimer’s disease and primary age-related tauopathy and the influence of comorbid neuropathologies. J Alzheimers Dis 2023;92(3):1037-49. PMID 36847012
75: Walker JM, Richardson TE, Farrell K, et al. Early selective vulnerability of the CA2 hippocampal subfield in primary age-related tauopathy. J Neuropathol Exp Neurol 2021;80(2):102-11. PMID 33367843
76: Wang X, Zhu K, Wu W, et al. Prevalence of mixed neuropathologies in age-related neurodegenerative diseases: a community-based autopsy study in China. Alzheimers Dement 2025;21(1):e14369. PMID 39582417
77: Whittington RA, Bretteville A, Dickler MF, Planel E. Anesthesia and tau pathology. Prog Neuropsychopharmacol Biol Psychiatry 2013;47:147-55. PMID 23535147
78: Wisniewski HM, Narang HK, Terry RD. Neurofibrillary tangles of paired helical filaments. J Neurol Sci 1976;27(2):173-81. PMID 129541
79: Wu W, Wang X, Xu Y, Ma C, Qian X, Qiu W. Neuropathological comorbidity, genetics and cognition in a Chinese community-based autopsy cohort. Brain 2025;148(7):2481-92. PMID 39901730
80: Yoshida K, Hata Y, Ichimata S, Tanaka R, Nishida N. Prevalence and clinicopathological features of primary age-related tauopathy (PART): a large forensic autopsy study. Alzheimers Dement 2024;20(8):5411-20. PMID 38938196
81: Yu L, Boyle PA, Leurgans S, Schneider JA, Bennett DA. Disentangling the effects of age and APOE on neuropathology and late life cognitive decline. Neurobiol Aging 2014;35(4):819-26. PMID 24199961

Contributors

All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.

Author

Peter T Nelson MD PhD

Dr. Nelson of the University of Kentucky has no relevant financial relationships to disclose.
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Editor

Howard S Kirshner MD

Dr. Kirshner of Vanderbilt University School of Medicine has no relevant financial relationships to disclose.
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Patient Profile

Age range of presentation: 65+ years
Sex preponderance: None selectively affected
Heredity: Heredity may be a factor. Crary and colleagues found that the MAPT locus that appears to be a risk factor for tauopathies in general is also a risk factors for more severe PART pathology (Crary et al 2014).
Population groups selectively affected: None
Occupation groups selectively affected: None

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PART (Primary age-related tauopathy)

Associated Disorders

Small-vessel pathologies
Limbic-predominant age-related TDP-43 proteinopathy (LATE)
Age-related tau astrogliopathy (ARTAG)

Differential Diagnosis

Alzheimer disease
Vascular cognitive impairment
Limbic-predominant age-related TDP-43 proteinopathy (LATE)
Age-related tau astrogliopathy (ARTAG)

Also Relevant

Alzheimer disease
Frontotemporal dementia
Memory loss

Clinical Categories

Neurobehavioral & Cognitive Disorders

PART (primary age-related tauopathy) …

PART (Primary age-related tauopathy)

Cite this article

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Clinical vignette

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Confusing conditions

Associated or underlying disorders

Diagnostic workup

Management

Special considerations

Pregnancy

Anesthesia

Media

References

Contributors

Author

Editor

Patient Profile

This is an article preview.
Start a Free Account
to access the full version.

Questions or Comment?

Also in This Category

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	• PART is apparently ubiquitous among older individuals but varies in severity and can be obscured by other pathologies.
	• The attributable risk of dementia due to PART is relatively low (compared to Alzheimer disease), so by itself, the natural history is a relatively benign downward cognitive trajectory in aging.

PART (Primary age-related tauopathy)

Cite this article

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Clinical vignette

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Confusing conditions

Associated or underlying disorders

Diagnostic workup

Management

Special considerations

Pregnancy

Anesthesia

Media

References

Contributors

Author

Editor

Patient Profile

This is an article preview. Start a Free Account to access the full version.

Questions or Comment?

Also in This Category

Cryptococcal meningitis

GM2 gangliosidoses

Developmental delay in children: evaluation and management

Levacetylleucine

Whipple disease

Mucopolysaccharidoses

Primary CNS angiitis

Cortical blindness

This is an article preview.
Start a Free Account
to access the full version.