Visualization of neurofibrillary tangle maturity in Alzheimer's disease: A clinicopathologic perspective for biomarker research

Christina M. Moloney, Val J. Lowe, Melissa E. Murray

Research output: Contribution to journalReview articlepeer-review

1 Scopus citations

Abstract

Neurofibrillary tangles, one of the neuropathologic hallmarks of Alzheimer's disease, have a dynamic lifespan of maturity that associates with progressive neuronal dysfunction and cognitive deficits. As neurofibrillary tangles mature, the biology of the neuron undergoes extensive changes that may impact biomarker recognition and therapeutic targeting. Neurofibrillary tangle maturity encompasses three levels: pretangles, mature tangles, and ghost tangles. In this review, we detail distinct and overlapping characteristics observed in the human brain regarding morphologic changes the neuron undergoes, conversion from intracellular to extracellular space, tau immunostaining patterns, and tau isoform expression changes across the lifespan of the neurofibrillary tangle. Post-translational modifications of tau such as phosphorylation, ubiquitination, conformational events, and truncations are discussed to contextualize tau immunostaining patterns. We summarize accumulated and emerging knowledge of neurofibrillary tangle maturity, discuss the current tools used to interpret the dynamic nature in the postmortem brain, and consider implications for cognitive dysfunction and tau biomarkers.

Original languageEnglish (US)
JournalAlzheimer's and Dementia
DOIs
StateAccepted/In press - 2021

Keywords

  • Alzheimer's disease
  • neurofibrillary tangles
  • neuropathology
  • tau
  • tau positron emission tomography

ASJC Scopus subject areas

  • Epidemiology
  • Health Policy
  • Developmental Neuroscience
  • Clinical Neurology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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