학술논문
Artificial intelligence-derived neurofibrillary tangle burden is associated with antemortem cognitive impairment
Document Type
article
Author
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
Source
Acta Neuropathologica Communications, Vol 10, Iss 1, Pp 1-12 (2022)
Subject
Language
English
ISSN
2051-5960
Abstract
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