From the Guidelines
Alzheimer's disease is characterized by neurofibrillary tangles in cortical neurons. These tangles are abnormal accumulations of a protein called tau that has become hyperphosphorylated, causing it to misfold and aggregate within neurons. Neurofibrillary tangles are one of the two major pathological hallmarks of Alzheimer's disease, alongside amyloid plaques. The tangles primarily affect neurons in the cerebral cortex, particularly in the entorhinal cortex and hippocampus early in the disease, before spreading to other cortical regions as the disease progresses. The presence of these tangles disrupts cellular transport systems, contributes to synaptic dysfunction, and eventually leads to neuronal death. While neurofibrillary tangles are most strongly associated with Alzheimer's disease, they can also be found in other neurodegenerative conditions such as chronic traumatic encephalopathy, progressive supranuclear palsy, and some forms of frontotemporal dementia, though with different distribution patterns or tau protein compositions.
Key points to consider:
- Neurofibrillary tangles are composed of hyperphosphorylated tau protein
- They are a hallmark of Alzheimer's disease, but can also be found in other neurodegenerative conditions
- The tangles primarily affect neurons in the cerebral cortex, particularly in the entorhinal cortex and hippocampus
- The presence of these tangles disrupts cellular transport systems, contributes to synaptic dysfunction, and eventually leads to neuronal death
According to the most recent study 1, Alzheimer's disease is characterized by amyloid pathology expressed as aggregated extracellular amyloid beta (Aβ)42 peptide and neurodegeneration due to intracellular neurofibrillary tangles composed of phosphorylated tau. This study highlights the importance of biomarkers in the diagnosis of Alzheimer's disease, including neurofibrillary tangles. Another study 1 also supports the idea that neurofibrillary tangles are a key feature of Alzheimer's disease, and that they can be used as a biomarker for the diagnosis of the disease.
In terms of diagnosis, the study 1 recommends the use of biomarkers, including neurofibrillary tangles, to establish support for the underlying etiology of the clinical syndrome in an individual with mild cognitive impairment (MCI). The study also notes that biomarkers can be used to determine the likelihood of cognitive and functional progression for an individual MCI patient to a more severe stage of MCI or to dementia.
Overall, the evidence suggests that neurofibrillary tangles are a key feature of Alzheimer's disease, and that they can be used as a biomarker for the diagnosis of the disease.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Disease Characterization
- Neurofibrillary tangles in cortical neurons are a characteristic feature of Alzheimer's disease, as evident from studies 2, 3, 4, 5, 6.
- The presence of neurofibrillary tangles and beta-amyloid deposits in the neocortex, hippocampus, and amygdala is a hallmark of Alzheimer's disease 2.
- These tangles are not only found in cortical neurons but also in subcortical glial cells in the frontal and temporal white matter 3.
Regional Vulnerability
- The formation of neurofibrillary tangles in Alzheimer's disease shows a preferential involvement of certain cytoarchitecturally defined cortical areas, suggesting systematic differences in regional neuronal vulnerability 4.
- The regional pattern of tangle density in Alzheimer's disease matches the pattern of neurons that retain their capacity for plastic remodeling in the adult brain 4.
Relationship with Cognitive Function
- Neurofibrillary tangles have a closer correlation with cognitive function than do amyloid plaques, particularly in the temporal lobe, which is associated with memory function 6.
- The presence of neurofibrillary tangles may reduce the risk of cell death in neurons, contrary to the prevailing hypothesis that tangles play a causal role in driving cognitive decline in Alzheimer's disease 5.