Primary age-related tauopathy
A neuropathological designation for tau tangles without amyloid plaques.
Primary age-related tauopathy, or PART, is a term coined in 2014 by a consortium of neuropathologists led by John F. Crary and Peter T. Nelson. It refers to neurofibrillary tangles found in the brains of both cognitively normal older adults and those with cognitive decline, occurring without the amyloid plaques characteristic of Alzheimer’s disease. The classification has been broadly accepted, with its defining criteria cited over 1,130 times by April 2023, despite some ongoing debate.
On autopsy, PART is marked by Alzheimer-like neurofibrillary tangles made of abnormal tau protein in neurons of the medial temporal lobe, but no accumulation of amyloid-beta peptide in plaques. This pattern leads to neuronal death and brain atrophy. Among cognitively normal elderly individuals, 18% show this pathology; among those with cognitive impairment, the figure is 5%. Severe cases of PART typically involve mild cognitive impairment or an amnestic dementia.
**Diagnostics**
*Neuropathological features* The tangles in PART are nearly identical to those seen in mild to moderate Alzheimer’s disease and other tauopathies. Amyloid pathology is sparse or absent; if a few senile plaques are present, Thal phase grading helps distinguish PART from Alzheimer’s.
*Clinical features* People with PART may be cognitively normal, mildly impaired, or demented. Higher tangle burdens (Braak stages III or IV) correlate with faster decline in episodic and semantic memory, processing speed, and attention. Braak stage 0 is limited to the cortex; stages I–II are confined to the transentorhinal region, progressing to the limbic system at stages III–IV. PART is categorized as symptomatic (with cognitive impairment or dementia) or asymptomatic. One hypothesis suggests PART-related dementia is rare in younger people but may emerge in the oldest old (over 90). Because the elderly population is growing rapidly, more research is needed to link PART pathology to specific clinical symptoms. Currently, no serological test exists for PART; MRI is the only available diagnostic tool.
**Relationship to Alzheimer’s disease** Because the tangle patterns are so similar, some scientists argue PART and Alzheimer’s are the same phenomenon. Others contend there is enough evidence to treat PART as a distinct pathological process. In Alzheimer’s, amyloid-beta 42 drives tau hyperphosphorylation and tangle f
- field
- Neuropathology
- known_for
- Designation of primary age-related tauopathy as a distinct neuropathological entity
- introduced
- 2014
Lore & Background
At autopsy, the hallmark of PART is the presence of Alzheimer-type neurofibrillary tangles composed of abnormal tau protein in neurons of the medial temporal lobe, with no amyloid-beta peptide accumulation in plaques. This leads to neuronal death and brain atrophy. 18% of Alzheimer neuropathological changes in cognitively normal and 5% of cognitively impaired elderly cases display this pattern. Patients with severe PART typically exhibit mild cognitive impairment or an amnestic dementia. Higher stages of tangle burden (Braak III or IV) are associated with more rapid decline in episodic and semantic memory, processing speed, and attention. PART can be categorized as symptomatic or asymptomatic, and one hypothesis suggests symptomatic onset may be infrequent in younger populations but more common in the oldest old (people greater than 90 years old).
Reader's Guide
PART is significant because it challenges the traditional view that neurofibrillary tangles in aging and dementia are always part of Alzheimer's disease. The absence of amyloid-beta plaques in PART suggests a distinct pathological process, with implications for developing diagnostics and therapeutics. Genetically, PART is associated with the MAPT H1 haplotype but not with APOE ε4, further supporting its separation from Alzheimer's disease. The controversy over whether PART represents a separate entity or a variant of Alzheimer's disease remains unresolved in the literature. Given that the elderly represent a fast-growing segment of the population worldwide, understanding PART's clinical symptoms and underlying mechanisms is critical. Current diagnostic tools are limited to MRI scans, as serological testing cannot identify PART patients. Research into tau regulation, including the role of miRNA-219 and kinases like MARK and GSK3β, may inform future treatments, though no therapies have been specifically linked to PART as of the source article.
Did You Know?
- PART was introduced in 2014 by a group of neuropathologists led by Drs. John F. Crary and Peter T. Nelson.
- 18% of cognitively normal elderly cases with Alzheimer-type changes show the PART pattern of degeneration.
- PART is associated with the MAPT H1 haplotype but not with APOE ε4, a gene strongly linked to Alzheimer's disease.
- MRI scans are the only currently available diagnostic tool for PART; serological testing cannot identify it.
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