| Autor: |
Gabriel A. Marx, Daniel G. Koenigsberg, Andrew T. McKenzie, Justin Kauffman, Russell W. Hanson, Kristen Whitney, Maxim Signaevsky, Marcel Prastawa, Megan A. Iida, Charles L. White, Jamie M. Walker, Timothy E. Richardson, John Koll, Gerardo Fernandez, Jack Zeineh, Carlos Cordon-Cardo, John F. Crary, Kurt Farrell, The PART working group |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Acta Neuropathologica Communications, Vol 10, Iss 1, Pp 1-12 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2051-5960 |
| DOI: |
10.1186/s40478-022-01457-x |
| Popis: |
Abstract Tauopathies are a category of neurodegenerative diseases characterized by the presence of abnormal tau protein-containing neurofibrillary tangles (NFTs). NFTs are universally observed in aging, occurring with or without the concomitant accumulation of amyloid-beta peptide (Aβ) in plaques that typifies Alzheimer disease (AD), the most common tauopathy. Primary age-related tauopathy (PART) is an Aβ-independent process that affects the medial temporal lobe in both cognitively normal and impaired subjects. Determinants of symptomology in subjects with PART are poorly understood and require clinicopathologic correlation; however, classical approaches to staging tau pathology have limited quantitative reproducibility. As such, there is a critical need for unbiased methods to quantitatively analyze tau pathology on the histological level. Artificial intelligence (AI)-based convolutional neural networks (CNNs) generate highly accurate and precise computer vision assessments of digitized pathology slides, yielding novel histology metrics at scale. Here, we performed a retrospective autopsy study of a large cohort (n = 706) of human post-mortem brain tissues from normal and cognitively impaired elderly individuals with mild or no Aβ plaques (average age of death of 83.1 yr, range 55–110). We utilized a CNN trained to segment NFTs on hippocampus sections immunohistochemically stained with antisera recognizing abnormal hyperphosphorylated tau (p-tau), which yielded metrics of regional NFT counts, NFT positive pixel density, as well as a novel graph-theory based metric measuring the spatial distribution of NFTs. We found that several AI-derived NFT metrics significantly predicted the presence of cognitive impairment in both the hippocampus proper and entorhinal cortex (p |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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