Table 1.

Neuropathology in FTLD-Tau Associated with MAPT Mutations

Mutation	Clinical	Neuropathology			Tau Isoforms	Referencesa	iPSCs Reported
		Macroscopy	Microscopy	Tauopathy
P301L	bvFTD, personality change, language abnormalities	atrophy of frontal and temporal lobes, basal ganglia, hippocampus, and depigmentation of substantia nigra	neuronal loss, ballooned neurons, and gliosis	neurons: tau-immunoreactive perinuclear, ring-like and dot-like cytoplasmic inclusions, fibrillary neuronal inclusions, and neuropil threads	4R	Mirra et al., 1999	Iovino et al., 2015, Paonessa et al., 2019, Silva et al., 2019
				astrocytes: thorn-shaped inclusions
				oligodendrocytes: coiled bodies
S305I	bvFTD, personality change, language abnormalities, Parkinsonism	atrophy of medial temporal lobe, temporal pole, and hippocampus	neuronal loss, gliosis, and ballooned neurons	neurons: tau-immunoreactive fibrillary inclusions and diffuse cytoplasmic staining	4R	Kovacs et al., 2008	N/A
				astrocytes: thorn-shaped inclusions
				oligodendrocytes: coiled bodies
				argyrophilic grains
S305N	bvFTD, personality change, memory loss	atrophy of frontal and temporal lobes	neuronal loss and gliosis	neurons: tau-immunoreactive Pick body-like and ring-like inclusions	4R	Boeve et al., 2005, Iijima et al., 1999	N/A
				astrocytes: thorn-shaped inclusions
				oligodendrocytes: coiled bodies
S305S	bvFTD, memory loss	atrophy of frontal and temporal lobes	neuronal loss, gliosis, and ballooned neurons	neurons: tau-immunoreactive neurofibrillary tangles and pretangles	4R	Skoglund et al., 2008, Stanford et al., 2000	N/A
				astrocytes: tuft-shaped inclusions
				oligodendrocytes: coiled bodies
IVS10+16	bvFTD, personality change, executive dysfunction, memory loss, parkinsonism, non-fluent aphasia	atrophy of frontal and temporal lobes, cingulate and insular cortex, hippocampus, striatum, amygdala and brainstem	neuronal loss, gliosis, and ballooned neurons	neurons: tau-immunoreactive fibrillary inclusions and diffuse cytoplasmic staining	4R	Janssen et al., 2002, Lantos et al., 2002	Espuny-Camacho et al., 2017, Esteras et al., 2017, Paonessa et al., 2019, Sposito et al., 2015
				astrocytes: thorn-shaped inclusions
				oligodendrocytes: coiled bodies
V337M	antisocial behavior, paranoia, executive dysfunction	atrophy of frontal and temporal lobes and hippocampus	neuronal loss and gliosis	neurons: tau-immunoreactive neurofibrillary tangles, pretangles, and neuropil threads	3R & 4R	Spillantini et al., 1996, Spina et al., 2017	Ehrlich et al., 2015, Sohn et al., 2019
				astrocytes: tuft-shaped inclusions
				oligodendrocytes: none
G389R	progressive aphasia, apathy, rigidity	atrophy of frontal and temporal lobes, hippocampus, and amygdala	neuronal loss and gliosis	neurons: tau-immunoreactive Pick body-like and filamentous inclusions	3R & 4R	Murrell et al., 1999	N/A
				astrocytes: none
				oligodendrocytes: none
R406W	memory loss	severe atrophy of frontal and temporal lobes and hippocampus	neuronal loss, gliosis, and ballooned neurons	neurons: tau-immunoreactive neurofibrillary tangles, Pick body-like inclusions	3R & 4R	Miyasaka et al., 2001, Reed et al., 1997	Imamura et al., 2016, Jiang et al., 2018
				astrocytes: thorn-shaped inclusions
				oligodendrocytes: coiled bodies
R406W/R406W	bvFTD	N/A	N/A	N/A	3R & 4R	Behnam et al., 2015, Ng et al., 2015	N/A

N/A, not available.

^aSee additional references at the AD/FTD Mutation Database (Cruts et al., 2012).