Primary age-related tauopathy (PART) is a neuropathologic entity defined by Alzheimer-type neurofibrillary tau pathology in medial temporal structures with absent or minimal amyloid-beta deposition.[1][2] PART is common in aging brains and is frequently identified in autopsy cohorts of older adults, including individuals without dementia.[1:1][3] The consensus framework positions PART as a tau-predominant age-related process that can contribute to cognitive impairment but is biologically distinct from typical Alzheimer disease when amyloid burden remains low.[2:1][4]
Consensus criteria define PART by combining tau stage (Braak NFT stage) and amyloid phase (Thal phase):[2:2]
This classification resolves older terminology such as "tangle-predominant senile dementia" and aligns clinicopathologic studies under a single standard.[1:2][2:3]
PART pathology centers on transentorhinal/entorhinal and hippocampal regions and may extend into limbic cortex with increasing Braak stage.[1:3][2:4] 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.[4:1][5]
Common findings include:[2:5][4:2]
Autopsy data indicate that PART is prevalent in advanced age and often coexists with other proteinopathies, complicating clinicopathologic attribution of symptoms.[3:1][6] Many individuals with low-stage PART remain cognitively intact, while higher tau burden and co-pathology increase risk of measurable impairment.[3:2][6:1][7]
Typical clinical profile when symptomatic:[6:2][7:1]
In vivo diagnosis remains challenging because currently deployed AD biomarkers are optimized for amyloid-positive Alzheimer biology.[8] PART-like cases often appear in A-/T+ or SNAP-like biomarker patterns depending on assay platform and stage.[8:1][9]
Differential diagnosis should prioritize:[2:6][8:2]
Unlike late-onset Alzheimer disease, PART does not show a strong, consistent APOE e4 enrichment across all cohorts; genetic architecture appears more heterogeneous and likely influenced by age-related resilience/vulnerability factors.[4:3][10] MAPT background may modulate tau burden, but definitive Mendelian PART genetics are not established.[4:4][10:1]
Standardized PART classification has practical implications for clinical trial interpretation and precision phenotyping in geriatric neurology:[2:7][8:3]
Priority research gaps include longitudinal biomarker validation, clinicopathologic prediction models, and intervention studies targeting tau-predominant aging phenotypes.[5:1][8:4]
Recent advances in Primary Age-Related Tauopathy (PART) have focused on understanding disease mechanisms, identifying biomarkers, and developing novel therapeutic approaches. Key developments include:
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Crary JF, Walker LC, Trojanowski JQ, et al. Consensus criteria for the neuropathologic diagnosis of primary age-related tauopathy (PART). Acta Neuropathologica. 2022. ↩︎ ↩︎ ↩︎ ↩︎ ↩︎ ↩︎ ↩︎ ↩︎
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Mattsson N, Insel PS, Palmqvist S, et al. Cerebrospinal fluid and plasma biomarkers in amyloid-negative tau-positive cognitive syndromes. Neurology. 2019. ↩︎
Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathologica. 1991. ↩︎ ↩︎