Table 1.
Summary and key features of primary and secondary tauopathies categorization.
| Clinical | Symptomology | Tau | Neuronal Pathology | Glia Pathology | Affected Brain Regions | |
|---|---|---|---|---|---|---|
| Primary Tauopathy | Pick’s disease (PiD) | Behavioral change, social disinhibition, eating disorder, absent/late parkinsonism. | 3R | Round cytoplasmic inclusions (Pick bodies), rare NFTs. | Ramified astrocytes. | Dentate gyrus of the hippocampus, frontal and temporal neocortical layers II, IV. Frontal, insular and anterior temporal cortices. |
| Behavioral variant of FTD (bvFTD) | Behavioral disinhibition, apathy, empathy loss, compulsiveness, executive and cognitive dysfunction. | 3R > 4R | Cytoplasmic NFTs, short dystrophic neurites. | Orbitofrontal, dorsolateral prefrontal, medial prefrontal cortices. Subcortical brain nuclei. Temporal-parietal lobes. | ||
| Progressive supranuclear palsy (PSP) | Apathy, anxiety, sleep disturbance. Spectrum from pure motor to pure cognitive presentations. | 4R | NFTs, neuropile threads. | Tufted astrocytes, somatodendritic coiled bodies. | Subthalamic nucleus, basal ganglia, brainstem. Posterior mesencephalic cortex. | |
| Corticobasal syndrome (CBS) | Asymmetric motor symptoms, apraxia, sensory impairment. Spectrum from pure motor to pure cognitive presentation. | 4R | NFTs, neuropile threads, ballooned neurons, pleomorphic inclusions (pre-tangles). | Annular clusters of short fuzzy cell processes, astrocytic Tau plaques, argyrophilic inclusions. | Frontoparietal cortex, striatum, substantia nigra. | |
| Argyrophilic grain disease (AGD) | Personality change, emotional imbalance, memory failure. | 4R | Argyrophilic grains, dendritic straight filaments and smooth tubules. | Thorn-shaped astrocytes, coiled bodies. | Medial temporal lobe, entorhinal cortex, hippocampus, amygdala. | |
| Aging-related Tau astrogliopathy (ARTAG) | Cognitive decline. | 4R | - | Thorn-shaped and granular-fuzzy astrocytes. | Medial temporal lobe, lobar (frontal, parietal, occipital, lateral temporal), subcortical, brainstem. | |
| Globular glial tauopathy (GGT) | Behavior change, cognitive decline, motor neuron disease (Parkinsonism). | 4R | - | Globular inclusions in astrocytes and oligodendrocytes. | White matter, limbic and isocortical regions. Hippocampus. | |
| Primary progressive aphasia (PPA) | Language deterioration, loss of semantic memory. | 3R, 4R | NFTs, amyloid plaques | Globular astrocytic inclusions. | Anterior and temporal lobes, parietal lobe. Frontoinsular cortex | |
| Primary age-related tauopathy (PART) | Cognitive impairment. | 3R, 4R | NFTs, neuropile threads | Medial temporal lobe. | Medial temporal lobe. | |
| Tangle-only dementia (TOD) | Late-onset dementia. | 3R, 4R | Intracellular PHFs, NFTs and neuropil threads. | Hippocampus. | ||
| Secondary Tauopathy | Alzheimer’s disease (AD) | Memory loss, cognitive dysfunction, social behavior changes. | 3R, 4R | NFTs, neuropile threads, neuritic plaques. | Entorhinal cortex, hippocampus, cerebral cortex. | |
| Chronic traumatic encephalop-athy (CTE) | Memory loss, confusion, personality/behavior changes. Motor decline. | 3R, 4R | P-Tau aggregates around small vessels, TDP-43 cytoplasmic inclusions. | P-Tau aggregates around small vessels. | Cortical sulci, isocortex layers II–III, hippocampus, subcortical nuclei. |