Dataset Information

Prevalence and clinicopathological features of primary age-related tauopathy (PART): A large forensic autopsy study.

ABSTRACT:

Introduction

Primary age-related tauopathy (PART), often regarded as a minimally symptomatic pathology of old age, lacks comprehensive cohorts across various age groups.

Methods

We examined PART prevalence and clinicopathologic features in 1589 forensic autopsy cases (≥40 years old, mean age ± SD 70.2 ± 14.2 years).

Results

PART cases meeting criteria for argyrophilic grain diseases (AGD) were AGD+PART (n = 181). The remaining PART cases (n = 719, 45.2%) were classified as comorbid conditions (PART-C, n = 90) or no comorbid conditions (pure PART, n = 629). Compared to controls (n = 208), Alzheimer's disease (n = 133), and AGD+PART, PART prevalence peaked in the individuals in their 60s (65.5%) and declined in the 80s (21.5%). No significant clinical background differences were found (excluding controls). However, PART-C in patients inclusive of age 80 had a higher suicide rate than pure PART (p < 0.05), and AGD+PART showed more dementia (p < 0.01) and suicide (p < 0.05) than pure PART.

Discussion

Our results advocate a reevaluation of the PART concept and its diagnostic criteria.

Highlights

We investigated 1589 forensic autopsy cases to investigate the features of primary age-related tauopathy (PART). PART peaked in people in their 60s in our study. Many PART cases over 80s had comorbid pathologies in addition to neurofibrillary tangles pathology. Argyrophilic grain disease and Lewy pathology significantly affected dementia and suicide rates in PART. Our results suggest that the diagnostic criteria of PART need to be reconsidered.

SUBMITTER: Yoshida K

PROVIDER: S-EPMC11350034 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Publications

Prevalence and clinicopathological features of primary age-related tauopathy (PART): A large forensic autopsy study.

Yoshida Koji K Hata Yukiko Y Ichimata Shojiro S Tanaka Ryo R Nishida Naoki N

Alzheimer's & dementia : the journal of the Alzheimer's Association 20240628 8

<h4>Introduction</h4>Primary age-related tauopathy (PART), often regarded as a minimally symptomatic pathology of old age, lacks comprehensive cohorts across various age groups.<h4>Methods</h4>We examined PART prevalence and clinicopathologic features in 1589 forensic autopsy cases (≥40 years old, mean age ± SD 70.2 ± 14.2 years).<h4>Results</h4>PART cases meeting criteria for argyrophilic grain diseases (AGD) were AGD+PART (n = 181). The remaining PART cases (n = 719, 45.2%) were classified as ...[more]

PMID: 38938196

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Project description:Primary age-related tauopathy (PART) is a form of Alzheimer-type neurofibrillary degeneration occurring in the absence of amyloid-beta (Aβ) plaques. While PART shares some features with Alzheimer disease (AD), such as progressive accumulation of neurofibrillary tangle pathology in the medial temporal lobe and other brain regions, it does not progress extensively to neocortical regions. Given this restricted pathoanatomical pattern and variable symptomatology, there is a need to reexamine and improve upon how PART is neuropathologically assessed and staged. We performed a retrospective autopsy study in a collection (n = 174) of post-mortem PART brains and used logistic regression to determine the extent to which a set of clinical and neuropathological features predict cognitive impairment. We compared Braak staging, which focuses on hierarchical neuroanatomical progression of AD tau and Aβ pathology, with quantitative assessments of neurofibrillary burden using computer-derived positive pixel counts on digitized whole slide images of sections stained immunohistochemically with antibodies targeting abnormal hyperphosphorylated tau (p-tau) in the entorhinal region and hippocampus. We also assessed other factors affecting cognition, including aging-related tau astrogliopathy (ARTAG) and atrophy. We found no association between Braak stage and cognitive impairment when controlling for age (p = 0.76). In contrast, p-tau burden was significantly correlated with cognitive impairment even when adjusting for age (p = 0.03). The strongest correlate of cognitive impairment was cerebrovascular disease, a well-known risk factor (p < 0.0001), but other features including ARTAG (p = 0.03) and hippocampal atrophy (p = 0.04) were also associated. In contrast, sex, APOE, psychiatric illness, education, argyrophilic grains, and incidental Lewy bodies were not. These findings support the hypothesis that comorbid pathologies contribute to cognitive impairment in subjects with PART. Quantitative approaches beyond Braak staging are critical for advancing our understanding of the extent to which age-related tauopathy changes impact cognitive function.

Project description:Neurodegenerative tauopathies are characterized by the deposition of distinct fibrillar tau assemblies whose rigid core structures correlate with defined neuropathological phenotypes. Essential tremor (ET) is a progressive neurological disease that, in some cases, is associated with cognitive impairment and tau accumulation. Consequently, we explored the tau assembly conformation in ET patients with tau pathology using cytometry-based tau biosensor assays. These assays quantify tau prion seeding activity present in brain homogenates based on conversion of intracellular tau-fluorescent protein fusions from a soluble to an aggregated state. Prions exhibit seeding barriers, whereby a specific assembly structure cannot serve as a template for a native monomer if the amino acids are not compatible. We recently exploited the tau prion species barrier to define tauopathies by systematically substituting alanine (Ala) in the tau monomer and measuring its incorporation into seeded aggregates within biosensor cells. The Ala scan precisely classified the conformation of tau seeds from diverse tauopathies. We next studied 18 ET patient brains with tau pathology. Only one case had concurrent high amyloid-β plaque pathology consistent with Alzheimer's disease (AD). We detected robust tau seeding activity in 9 (50%) of the patients. This predominantly localized to the temporal pole and temporal cortex. We examined 8 ET cases with the Ala scan and determined that the amino acid requirements for tau monomer incorporation into aggregates seeded from these ET brain homogenates were identical to those of AD and primary age-related tauopathy (PART), and completely distinct from other tauopathies such as corticobasal degeneration, chronic traumatic encephalopathy, and progressive supranuclear palsy. Based on these studies, tau assembly cores in a pathologically confined subset of ET cases with high tau pathology are identical to AD and PART. This could facilitate more precise diagnosis and therapy for ET patients with cognitive impairment.

Dataset Information

Prevalence and clinicopathological features of primary age-related tauopathy (PART): A large forensic autopsy study.

Introduction

Methods

Results

Discussion

Highlights

Publications

Prevalence and clinicopathological features of primary age-related tauopathy (PART): A large forensic autopsy study.

Similar Datasets

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