Primary age-related tauopathy (PART) is a distinct neurodegenerative condition primarily affecting older adults and contributing to cognitive decline. It is characterized by the accumulation of tau protein tangles within specific brain regions. The term PART was introduced in 2014 to describe these neurofibrillary tangles, distinct from Alzheimer’s disease’s amyloid plaques. In individuals with severe PART, mild cognitive impairment or a form of amnestic dementia is observed.
Understanding Tau Protein and Its Role
Tau protein, in a healthy brain, stabilizes microtubules within neurons. Microtubules are structures that help maintain the neuron’s shape and transport materials throughout the cell. In PART, tau undergoes hyperphosphorylation, where too many phosphate groups attach to the protein.
This hyperphosphorylation causes tau to detach from the microtubules, leading to their destabilization and breakdown. The unbound tau then clumps together, forming insoluble aggregates known as neurofibrillary tangles. These tangles disrupt normal neuronal functioning, contributing to their dysfunction and eventual loss. The presence of these tangles can ultimately lead to neuronal death and brain atrophy.
How PART Differs from Other Conditions
Distinguishing PART from other neurodegenerative conditions, especially Alzheimer’s Disease (AD), is important because both involve tau pathology. While tau tangles are present in both, a key difference in PART is the absence or minimal presence of amyloid-beta plaques, a hallmark of AD. In PART, tau tangles are mostly confined to the medial temporal lobe and brainstem, unlike the broader distribution seen in AD.
PART presents with a more isolated and milder cognitive decline, primarily affecting memory, compared to the wider range of impairments observed in AD. The clinical course of PART is more moderate and less devastating than that of AD. While other primary tauopathies like progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) also involve abnormal tau protein, their specific pathological distribution and clinical presentations differ.
Recognizing Symptoms and Progression
The cognitive symptoms associated with PART involve memory impairment, specifically episodic memory loss. These symptoms begin subtly and progress more slowly compared to typical Alzheimer’s disease. The progression of cognitive impairment can vary among individuals, with some experiencing a gradual decline over several years.
The disease can start with mild cognitive impairment (MCI), where individuals experience a noticeable decline in memory or thinking skills but can still manage daily routines independently. While MCI can precede dementia, it does not always progress to that stage. Significant non-cognitive symptoms, such as motor deficits or prominent behavioral changes, are not characteristic of pure PART.
Current Diagnosis and Management
Diagnosing PART in living individuals presents challenges, as it is a diagnosis of exclusion or confirmed through post-mortem examination. The diagnostic process involves clinical assessments and detailed neuropsychological testing to evaluate cognitive functions like attention, judgment, and memory. These tests help objectively confirm cognitive impairment and identify specific areas of decline.
Brain imaging, such as MRI, is used to rule out other causes of cognitive decline and to observe patterns of brain atrophy consistent with PART. Research is ongoing into biomarkers like specific tau PET imaging or cerebrospinal fluid (CSF) markers, which may eventually aid in live diagnosis by detecting tau pathology in the absence of amyloid-beta. Currently, there is no specific cure or disease-modifying treatment for PART. Care focuses on symptomatic and supportive approaches, including cognitive rehabilitation aimed at improving cognitive abilities and daily functioning. Lifestyle interventions, such as physical exercise and a healthy diet, are also encouraged, along with managing co-existing health conditions to enhance overall quality of life.