Primary age-related tauopathy

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.

Clinical features

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.

Relationship to Alzheimer's disease

Currently, no serological test exists for PART; MRI is the only available diagnostic tool. 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.