Primary age-related tauopathy (PART) is a neuropathologic entity defined by Alzheimer-type neurofibrillary [tau](/proteins/tau) pathology in medial temporal structures with absent or minimal [amyloid-beta](/proteins/amyloid-beta) deposition.[@crary2014][@crary2022] PART is common in aging brains and is frequently identified in autopsy cohorts of older adults, including individuals without dementia.[@crary2014][@nelson2019] The consensus framework positions PART as a [tau](/proteins/tau)-predominant age-related process that can contribute to cognitive impairment but is biologically distinct from typical Alzheimer disease when amyloid burden remains low.[@crary2022][@jellinger2015]
Core Diagnostic Concept
Consensus criteria define PART by combining [tau](/proteins/tau) stage (Braak NFT stage) and amyloid phase (Thal phase):[@crary2022]
Definite PART: Braak stage I-IV tau pathology with Thal amyloid phase 0
Possible PART: Braak stage I-IV tau pathology with limited amyloid deposition (low Thal phase)
Cases with substantial amyloid deposition are generally classified within the Alzheimer disease neuropathologic continuum rather than PART
This classification resolves older terminology such as "tangle-predominant senile dementia" and aligns clinicopathologic studies under a single standard.[@crary2014][@crary2022]
Neuropathology
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Primary Age-Related Tauopathy (PART)
Overview
Primary age-related tauopathy (PART) is a neuropathologic entity defined by Alzheimer-type neurofibrillary [tau](/proteins/tau) pathology in medial temporal structures with absent or minimal [amyloid-beta](/proteins/amyloid-beta) deposition.[@crary2014][@crary2022] PART is common in aging brains and is frequently identified in autopsy cohorts of older adults, including individuals without dementia.[@crary2014][@nelson2019] The consensus framework positions PART as a [tau](/proteins/tau)-predominant age-related process that can contribute to cognitive impairment but is biologically distinct from typical Alzheimer disease when amyloid burden remains low.[@crary2022][@jellinger2015]
Core Diagnostic Concept
Consensus criteria define PART by combining [tau](/proteins/tau) stage (Braak NFT stage) and amyloid phase (Thal phase):[@crary2022]
Definite PART: Braak stage I-IV tau pathology with Thal amyloid phase 0
Possible PART: Braak stage I-IV tau pathology with limited amyloid deposition (low Thal phase)
Cases with substantial amyloid deposition are generally classified within the Alzheimer disease neuropathologic continuum rather than PART
This classification resolves older terminology such as "tangle-predominant senile dementia" and aligns clinicopathologic studies under a single standard.[@crary2014][@crary2022]
Neuropathology
PART pathology centers on transentorhinal/entorhinal and hippocampal regions and may extend into limbic [cortex](/brain-regions/cortex) with increasing Braak stage.[@crary2014][@crary2022] Tau biochemistry overlaps with Alzheimer-type paired helical filament tau, but the burden and network spread are usually more restricted than in advanced Alzheimer disease.[@jellinger2015][@josephs2017]
Common findings include:[@crary2022][@jellinger2015]
Neurofibrillary tangles and neuropil threads in medial temporal lobe
Relative sparing of neocortical amyloid plaque pathology
Frequent co-pathology in late life (e.g., cerebrovascular disease, Lewy pathology, LATE-NC)
Epidemiology and Clinical Phenotype
Autopsy data indicate that PART is prevalent in advanced age and often coexists with other proteinopathies, complicating clinicopathologic attribution of symptoms.[@nelson2019][@jicha2006] Many individuals with low-stage PART remain cognitively intact, while higher tau burden and co-pathology increase risk of measurable impairment.[@nelson2019][@jicha2006][@robinson2018]
Typical clinical profile when symptomatic:[@jicha2006][@robinson2018]
Mild episodic memory and executive dysfunction
Slower progression than biomarker-confirmed Alzheimer disease in many cohorts
Heterogeneous phenotype driven by co-pathology burden
Biomarkers and Differential Diagnosis
In vivo diagnosis remains challenging because currently deployed AD biomarkers are optimized for amyloid-positive Alzheimer biology.[@jack2018] PART-like cases often appear in A-/T+ or SNAP-like biomarker patterns depending on assay platform and stage.[@jack2018][@mattsson2019]
Differential diagnosis should prioritize:[@crary2022][@jack2018]
Unlike late-onset Alzheimer disease, PART does not show a strong, consistent [APOE](/proteins/apoe-protein) e4 enrichment across all cohorts; genetic architecture appears more heterogeneous and likely influenced by age-related resilience/vulnerability factors.[@jellinger2015][@braak1991] [MAPT](/genes/mapt) background may modulate tau burden, but definitive Mendelian PART genetics are not established.[@jellinger2015][@braak1991]
Clinical and Research Implications
Standardized PART classification has practical implications for clinical trial interpretation and precision phenotyping in geriatric neurology:[@crary2022][@jack2018]
Improves separation of amyloid-independent tau biology from AD-targeted cohorts
Supports stratification of mixed pathology in aging studies
Helps explain discordance between tau pathology and clinical syndrome severity
Priority research gaps include longitudinal biomarker validation, clinicopathologic prediction models, and intervention studies targeting tau-predominant aging phenotypes.[@josephs2017][@jack2018]
[Allen Brain Atlas - Aging, Dementia & TBI](https://aging.brain-map.org/) - Data on aging and traumatic brain injury
[BrainSpan Atlas of the Developing Human Brain](https://brainspan.org/) - Developmental gene expression data
References
[Crary JF, Trojanowski JQ, Schneider JA, et al, Primary age-related tauopathy (PART): a common pathology associated with human aging (2014)](https://pubmed.ncbi.nlm.nih.gov/25348064/)
[Crary JF, Walker LC, Trojanowski JQ, et al, Consensus criteria for the neuropathologic diagnosis of primary age-related tauopathy (PART) (2022)](https://pubmed.ncbi.nlm.nih.gov/35503043/)
[Nelson PT, Abner EL, Schmitt FA, et al, Defining and phenotyping age-related tauopathy in the context of cognitive decline (2019)](https://pubmed.ncbi.nlm.nih.gov/30874984/)
[Jellinger KA, Attems J, Primary age-related tauopathy versus Alzheimer disease: similarities and differences (2015)](https://pubmed.ncbi.nlm.nih.gov/26486986/)
[Josephs KA, Whitwell JL, Tosakulwong N, et al, Tau PET and neuropathology correlations in aging-related tau pathology (2017)](https://pubmed.ncbi.nlm.nih.gov/29272362/)
[Jicha GA, Schmitt FA, Abner E, et al, Neuropathologic outcome of mild cognitive impairment in the elderly (2006)](https://pubmed.ncbi.nlm.nih.gov/16717255/)
[Robinson JL, Corrada MM, Kawas CH, et al, Non-Alzheimer's contributors to dementia and resilience in the oldest-old (2018)](https://pubmed.ncbi.nlm.nih.gov/29691577/)
[Jack CR Jr, Bennett DA, Blennow K, et al, NIA-AA Research Framework: toward a biological definition of Alzheimer's disease (2018)](https://pubmed.ncbi.nlm.nih.gov/29653606/)
[Mattsson N, Insel PS, Palmqvist S, et al, Cerebrospinal fluid and plasma biomarkers in amyloid-negative tau-positive cognitive syndromes (2019)](https://pubmed.ncbi.nlm.nih.gov/31152727/)
[Braak H, Braak E, Neuropathological stageing of Alzheimer-related changes (1991)](https://pubmed.ncbi.nlm.nih.gov/1759558/)