Table 4.

Characteristic pathological features

	Main pathology	Histopathological findings	Areas of atrophy and neuronal loss; further characteristics
MSA	α-synucleinopathy	α-synuclein(+) oligodendrocytic glial cytoplasmic inclusions (GCIs); α-synuclein(+) neuronal cytoplasmic and intranuclear inclusions; myelin loss	Atrophy in putamen, pons, middle cerebellar peduncle, cerebellum; neuronal loss in putamen, substantia nigra, inferior olivary nucleus, Onuf’s nucleus, intermediolateral cell column; demyelination – striato-pallidal fibers, transverse pontine fibers, olivocerebellar fibers, cerebellar white matter
PSP	4R tauopathy	Tau(+) neurofibrillary globose tangles (4R tau); tufted astrocytes with tau(+) inclusions; tau(+) coiled bodies in oligodendrocytes; thread-like structures (diencephalon, brainstem)	Atrophy of midbrain, superior cerebellar peduncle, prefrontal cortex; neuronal loss in subthalamic nucleus, substantia nigra, cerebellar dentate nucleus; loss of pigment in substantia nigra
CBD	4R tauopathy	Astrocytic plaques (4R tau in terminal processes); pleomorphic tau(+) cortical neuronal inclusions, achromatic ballooned neurons; pretangles (tau(+) cytoplasmic inclusions in neurons); coiled bodies (less than in PSP); sparse tau(+) oligodendroglial lesions; dense, widespread thread-like structures in gray and white matter (neuropil threads)	Atrophy of superior frontal, superior parietal and motor cortices, SMA, perisylvian region, corpus callosum; neuronal loss in globus pallidum, substantia nigra, subthalamic nucleus; loss of pigment in substantia nigra
FTLD-tau	3R, 4R or 3R + 4R tauopathies	Tau(+) cytoplasmic inclusions in neurons and glia Pick’s disease: 3R tau(+) neuronal cytoplasmatic inclusions (Pick bodies); ballooned neurons (Pick cells); sparse glial inclusions Argyrophilic grain disease: 4R tau(+) grains, oligodendroglial coiled bodies, ballooned neurons NFT dementia: 3R + 4R tau(+) neuronal inclusions (neurofibrillary tangles)	Bilateral atrophy with neuronal loss and astrogliosis of frontal and temporal cortices, including medial temporal regions, spreading to more posterior areas (parietal cortex) in disease course
FTLD-TDP	TDP-43 proteinopathy	TDP-43(+), ubiquitin(+), p62-sequestosome(+) neuronal cytoplasmic and intranuclear inclusions; oligodendroglial and astrocytic inclusions; superficial cortical laminar spongiosis subtypes A, B, C and D	Cortical atrophy (frontal > temporal and parietal lobes), hippocampus, amygdala, basal ganglia (caudate > putamen > globus pallidus)
FTLD-TDP with C9orf72 mutation	TDP-43 proteinopathy	TDP-43(+) inclusions; in addition to TDP-43 pathology: dipeptide repeat protein(+), ubiquitin(+), p62-sequestosome(+) neuronal and glial inclusions (cerebellar granule cells); nuclear RNA foci	Cortical atrophy (frontal > temporal and parietal lobes), motor cortex (some cases), hippocampus, amygdala, basal ganglia (caudate > putamen > globus pallidus); neuronal loss in brainstem, spinal cord motor neurons
FTLD-FET	Ubiquitinopathy	FUS(+), ubiquitin(+), p62-sequestosome(+) neuronal cytoplasmic and neuronal intranuclear inclusions	Cortical atrophy (frontal > temporal and parietal lobes), striatal atrophy (severe)