Journal
ALZHEIMERS & DEMENTIA
Volume 17, Issue 9, Pages 1554-1574Publisher
WILEY
DOI: 10.1002/alz.12321
Keywords
Alzheimer' s disease; neurofibrillary tangles; neuropathology; tau positron emission tomography; tau
Categories
Funding
- Alzheimer's Association [AARG-17-533458]
- National Institute on Aging [R01 AG054449, U01 AG57195, P30 AG062677]
- Florida Department of Health
- Ed and Ethel Moore Alzheimer's Disease Research Program [8AZ06, 20a22]
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Neurofibrillary tangles, a hallmark of Alzheimer's disease, undergo a dynamic process of maturity that impacts neuron biology and cognitive function. The levels of maturity include pretangles, mature tangles, and ghost tangles, with distinct characteristics observed through tau protein immunostaining and morphologic changes. Post-translational modifications of tau play a significant role in therapeutic targeting strategies for cognitive dysfunction.
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.
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