Table 3.

Clinical, radiological, and pathological clues for GGT, AGD, and PiD.

Disease entity	Clinical features	Radiology	Pathology
GGT (28, 115, 116) (4R-tauopathy)	• Can clinically present with bvFTD (Type 1), PSP/CBS with MND/PLS spectrum (Type 2) and mixed (Type 3), based on topographic location of white matter deposits of tau immunoreactive globular glial inclusions (117) • Atypical PSP with marked upper motor neuron (UMN) signs (PSP-PLS phenotype) can be a clinical clue • Other phenotypes: PPA-G with chorea (118), PPA-S (119), Mill's hemiplegic variant of MND (120)	• Frontotemporal atrophy with T2 FLAIR hyperintensities in white matter involving cortical-white matter junctions, subcortical and periventricular areas, anterior commissure, posterior horn of lateral ventricles, cerebral peduncle, basis pontis (regions corresponding to traversing corticospinal fibers) (28, 120, 121)	Tau-immunoreactive globular inclusions in astrocytes (GAI) and oligodendrocytes (GOI) (117, 122) • Type 1: frontotemporal involvement • Type 2: motor cortex and/or corticospinal tract involvement • Type 3: frontotemporal, motor cortex and/or corticospinal tract involvement
AGD (123, 124)(4R-tauopathy)	• Limbic predominant 4R-tauopathy that commonly presents with very late onset (>75 year) slowly progressive mild cognitive impairment with prominent psychiatric symptoms (limbic involvement), disinhibited behaviors, change of appetite and eating disorders (hypothalamic involvement), late-onset schizophrenia and delusional disorders, late-onset bipolar disorder • AGD can be seen in very late onset CBD, PSP • CBD-Cog patients have found to have more AGD pathology than CBD-CBS (37) • Other phenotypes: Late onset Parkinson's disease with dementia, hallucination, delusion, mimicking Lewy body dementia (DLB) (125, 126), bvFTD presentation with diffuse cortical involvement (127) • Can rarely present with rapid cognitive decline, seizure, psychotic episodes, urinary incontinence in younger population (<75 year), mimicking prion disease (128)	• Medial temporal lobe atrophy • Midbrain atrophy if associated PSP pathology	• Argyrophilic grains spindle- or comma-shaped Gallyas positive, 4R tau in neuronal dendrites and axons • CBD, PSP, and AD pathology are commonly associated
PiD (129, 130) (3R-tauopathy)	• bvFTD (most common presentation), sometimes can present as PPA-S	• bvFTD: Frontal (predominantly medial frontal cortex and also involving dorsolateral and orbitofrontal regions) >temporal atrophy (131) • PPA-S: mainly left anterior temporal lobe, with involvement of inferior temporal gyrus, fusiform gyrus, anterior hippocampal region (113, 131)	Pick bodies, Pick cells, ramified astrocytes