Table 1 Neurodegenerative diseases with tau inclusions

Alzheimer’s disease

Neurofibrillary tangles (NFTs) found in neocortex and limbic regions. Intracellular NFTs are found to be both 3R and 4R tau-positive with a preferential shift to 3R immunoreactivity in extracellular NFTs.

Amyotrophic lateral sclerosis of Guam

NFTs positive for 3R and 4R found in neocortex and limbic areas with a predilection for cortical layers II and II.

Argyrophilic grain disease

Spindle-shaped, 4R tau-positive lesions accumulate in neuronal processes. Grains are typically found in the neuropil of limbic areas, but can be found diffusely deposited in cortex. Coiled bodies in oligodendrocytes and tau-positive pretangles can be abundantly found.

Chronic traumatic encephalopathy

Widespread NFTs, tau-immunoreactive astrocytic inclusions, and neuritic pathology can be found with a predilection for superficial cortical layers and sulcal depths. Irregular, patchy tau pathology observed in cortex.

Corticobasal degeneration

4R tau-positive ballooned neurons, astrocytic plaques, and neuropil threads are found in both gray and white matter of cortical and striatal regions.

Diffuse neurofibrillary tangles with calcification

NFTs and neuropil threads found diffusely deposited in frontal and temporal cortex, as well as limbic areas.

Down’s syndrome

NFTs and granulovaculoar degeneration can be found in the hippocampus.

Familial British dementia

NFTs and neuropil threads found relatively restricted to limbic regions.

Familial Danish dementia

NFTs and neuropil threads found in limbic with abnormal neurites limited to amyloid-laden blood vessels and variable involvement of cortical regions.

Frontotemporal dementia and parkinsonism linked to chromosome 17 (caused by MAPT mutations)

Widespread neuronal and glial cytoplasmic inclusions immunopositive for 3R, 3+4R, or 4R tau. Morphology of lesions varies with reportedly observed coiled bodies, tufted astrocytes, and astrocytic plaques.

Frontotemporal lobar degeneration (some cases caused by C9ORF72 mutations)

NFT pathology can be found in a similar Alzheimer’s-like limbic and cortical distribution.

Gerstmann–Sträussler–Scheinker disease

Tau pathology can be absent, not reported, or inconsistently reported as widespread neurofibrillary pathology depending on the PRNP mutation.

Guadeloupean parkinsonism

Widespread neurofibrillary pathology can be found as NFTs, neuropil threads, and astrocytic tufts.

Myotonic dystrophy

NFTs in limbic and brainstem regions.

Neurodegeneration with brain iron accumulation

Diffuse neuritic pathology in cortex, but rare NFT pathology.

Niemann–Pick disease, type C

NFTs, neuropil threads, and oligodendroglial coiled bodies range from transentorhinal confinement to widespread limbic and cortical involvement.

Non-Guamanian motor neuron disease with neurofibrillary tangles

NFTs can be found in limbic structures, midbrain, and pontine nuclei.

Parkinsonism–dementia complex of Guam

NFTs positive for 3R and 4R found in cortical areas with a predilection for cortical layers II and III. Tau pathology is also found in limbic, basal ganglia, brainstem, and spinal cord. Granular hazy tau inclusions are found in motor cortex, amygdala, and inferior olivary nucleus.

Pick’s disease

Widespread spherical cytoplasmic 3R tau-positive inclusions (Pick bodies) can be found in hippocampus, basal ganglia, brainstem nuclei, and especially cortex.

Postencephalitic parkinsonism

Widespread tau-positive neuronal and glial lesions. Globose NFTs are a prominent feature in brainstem nuclei, especially substantia nigra and locus coeruleus. NFTs are more common in limbic structures than cortex, and have a predilection for layers II and III.

Progressive supranuclear palsy

4R tau-positive globose NFTs, tufted astrocytes, and coiled bodies are often found in the subthalamic nucleus, globus pallidus, ventral thalamus, cerebellar dentate nucleus, and variable involvement of cortex.

SLC9A6-related mental retardation

Glial tau pathology, resembling coiled bodies, can be found in brainstem and cerebellar white matter tracts. Astrocytic plaques can also be found in brainstem, thalamus, and cerebral white matter. NFT-like inclusions can be found in brainstem and thalamic nuclei, hippocampus, and cortex.

Subacute sclerosing panencephalitis

Glial fibrillary tangles can be found in oligodendroglia. NFTs can be found differentially distributed in hippocampus and/or cerebral cortex.

Tangle predominant dementia

4R predominant NFT accumulation relatively combined to limbic regions.

White matter tauopathy with globular glial inclusions

Widespread globular oliogdendroglial inclusions, less so in astroglial, immunoreactive for 4R-tau.