Table 1.
Overview of the most prevalent tauopathies.
| Disease | Tau lesion type | Lesion distribution | Phenotype | Reference |
|---|---|---|---|---|
| Alzheimer’s disease | Neurofibrillary tangles Neuritic component of plaques Neuropil threads 3R+4R tau |
Allocortex, limbic regions, most neocortical fields except motor cortex, brainstem (locus coeruleus, raphe nuclei) | Predominantly amnestic, w. disorientation in time and space. Language, dysexecutive, and visual variant exist. Multiple domains impaired in dementia. | Pathology: (Braak and Braak, 1991) Clinics: (Morris et al., 2014; Jack et al., 2018) |
| Argyrophilic grain disease | Argyrophilic grains, pre-neurofibrillary tangles in neurons and coiled bodies in oligodendrocytes 4R tau |
Mainly entorhinal cortex and hippocampus, insula, amygdala, hypothalamus, cingulated gyrus, … | Amnestic and multi-domain cognitive impairment. Behavioral abnormalities and FTD-like symptoms possible. | Pathology: (Grinberg and Heinsen, 2009) Clinics:(Rodriguez et al., 2016) |
| Chronic traumatic encephalopathy | Neurofibrillary tangles and neurites, astrocytic tangles 3R+4R tau |
Focal (perivascular) epicenters, amygdala, hippocampus, nucleus basalis of Meynert, substantia nigra, locus coeruleus | Mainly executive function, behavior, and short-term memory impaired | Pathology: (McKee et al., 2013) Clinics: (McKee et al., 2013) |
| Corticobasal degeneration | Pre-tangles Astrocytic plaques thread-like lesions, corticobasal bodies, and coiled bodies 4R tau |
Basal ganglia, thalamus, focal parietal, mostly asymmetric, and brainstem | Asymmetric levodopa-resistant parkinsonism, postural instability, dystonia, myoclonus. Behavioral changes, aphasia, cognitive impairment. Cortical sensory loss. Alien limb. | Pathology: (Josephs et al., 2011) Clinics: (Armstrong et al., 2013; Levin et al., 2016) |
| Dementia in Down syndrome | Similar to AD | Similar to AD | Similar to AD, complicated by existing cognitive disability | Pathology: (Hof et al., 1995) Clinics: (Ghezzo et al., 2014) |
| Frontotemporal lobar degeneration (w./w.o. Parkinsonism) | (extremely varied) 3R, 4R, or 3R+4R tau |
Frontal and temporal/temporoparietal neocortex, (substantia nigra) | Language (PPA), behavior, executive function (bvFTD), possibly parkinsonism (FTDP-17) | Pathology: (Seilhean et al., 2011) Clinics: (Wszolek et al., 2006; Gorno-Tempini et al., 2011) |
| Pick’s disease | Pick bodies Astroglial processes 3R tau |
Frontal and temporal neocortex, dentate gyrus, deep gray matter and brainstem (monoaminergic nuclei) | Language, behavior, executive function (as bvFTD or PPA) | Pathology: (Sieben et al., 2012) Clinics: (Hodges et al., 2004; Warren et al., 2013) |
| Progressive supranuclear palsy | Globose NFTs Tufted astrocytes 4R tau |
Predominantly in basal ganglia, subthalamic nucleus, and substantia nigra. Involvement of motor cortex and cerebellum (e.g., superior cerebellar peduncle). | Vertical supranuclear gaze palsy, postural instability, falls, pseudobulbar palsy, rigidity, akinesia; behavior, executive function, and language impaired; Parkinsonism |
Pathology: (Josephs et al., 2011) Clinics: (Levin et al., 2016; Respondek and Hoglinger, 2016) |
| Tangle-only dementia | Neurofibrillary tangles Neuropil threads Ghost tangles 3R+4R tau 4R→3R shift during tangle maturation |
Allocortex and medial temporal lobe, limbic regions; subcortical: locus coeruleus, nucleus basalis of Meynert, amygdala | Mainly memory deficit; slower progression than AD | Pathology and Clinics: (Jellinger and Bancher, 1998; Jellinger and Attems, 2007) |
Most common lesion distribution patterns listed. Coexistence of tau pathology with multiple other pathologies is possible. The listed phenotype mentions possible clinical manifestations; not all signs are required for diagnosis. Lesser amounts of 3R-tau can be found in 4R-tau dominated pathologies, and vice versa.