Table 2.

Description of neuropathology/tau-pathology in nine patients with anti-IgLON5 disease

Patient	Tau-pathology
1	Brainstem predominant PSP Neuronal and glial tauopathy in the thalamus, tegmentum and the basis of the brainstem, 4R tau positive tangles and neuropil threads, coiled bodies and tufted astrocytes, compatible with PSP, 3R tau was negative. Amyloid plaques were absent. pTDP43 inclusions absent
2 [4]	Age-related neurofibrillary pathology Neuropil threads and sparse neuronal tangles in dorsomedial and ventromedial nuclei. Also, in Locus coeruleus, mixture of 3R and 4R isoforms, neurofibrillary tangles, pre-tangles and neuropil threads in all hippocampal regions, especially CA2 and entorhinal cortex. Amyloid beta absent, α-synuclein absent, pTDP43: neuronal skein-like and granular cytoplasmic inclusions in the thalamus, striatum, midbrain, also in parenchymal ramified microglial cells and in perivascular microglia in the thalamus, hippocampus, striatum, nucleus basalis, midbrain
3 [5]	Age-related neurodegenerative pathology Neurofibrillary pathology and β-amyloid deposits consistent with Alzheimer’s disease of intermediate severity (Braak neurofibrillary stage III, Thal phase 4, CERAD plaque score B; Alzheimer´s disease neuropathological changes A3,B2,C2)
4 [14]	Classical IgLON5-related brainstem tauopathy Prominent tauopathy (4R and 3R) characterized by numerous Gallyas-positive neurofibrillary tangles, diffuse granular cytoplasmic phospho-tau (pTau; AT8) immunoreactivity (pre- tangles), and neuropil threads involving predominantly the hypothalamus, zona incerta, hippocampus, tegmentum of the brainstem (mesencephalon, pons, and medulla), and cervical spinal cord
5 [24]	Classical IgLON5-related brainstem tauopathy pTau (AT8) pathology in the hippocampus, entorhinal cortex, N. basalis Meynert, substantia innominata, septal nuclei, hypothalamus, in the brainstem, isolated pTau pathology in the ant. cingulate cortex, amygdala, pallidum, thalamus, subthalamic nucleus, substantia nigra, dentate nucleus, cervical spinal cord. 3R and 4R tau isoforms present
6 [24]	Classical IgLON5-related brainstem tauopathy pTau (AT8) pathology in the hippocampus, entorhinal cortex, amygdala, N. basalis Meynert, substantia innominata, zona incerta, subthalamic nucleus, hypothalamus, brainstem, isolated pTau pathology in the striatum, pallidum, ant. cingulate cortex, thalamus, corpus mamillare, substantia nigra, dentate nucleus, cervical spinal cord. 3R and 4R tau isoforms present. pTDP43: some neuronal skein-like, small compact or diffuse granular inclusions in neurons of the brainstem and spinal cord
7	Age-related neurodegenerative pathology Neurofibrillary pathology restricted to limbic system (Braak III), few neuritic plaques (CERAD Score B) and Thal phase 4 (Alzheimer´s disease neuropathological changes A3,B2,C2), moderate vascular amyloidosis, ARTAG, granular fuzzy astrocytes, few Lewy-type/alpha-synuclein neurites in the olfactory system (olfactory-only)
8 [22]	Probable anti-IgLON5 disease—classical IgLON5-related brainstem tauopathy pTau (AT8) pathology in the hippocampus, entorhinal cortex, amygdala, N. basalis Meynert, substantia innominata, zona incerta, hypothalamus, brainstem, cervical spinal cord; isolated tau pathology in the subthalamic nucleus, thalamus, striatum, corpus mamillare. 3R and 4R tau isoforms present
9	Classical IgLON5-related brainstem tauopathy pTau (AT8) pathology in the hypothalamus, brainstem tegmentum, medulla oblongata with neuronal cell loss, gliosis, microglia activation with tau positive tangles and neurites. 3R and 4R tau isoforms present. Mild brainstem predominant Lewy body/alpha-synuclein pathology; small vessel disease