Table 2

Stages, phases and patterns reported for various α-synuclein and TDP-43 pathologies

TDP-43 (bvFTD)151 Orbital gyri, gyrus rectus and amygdala.Pattern I
Middle frontal and anterior cingulate gyrus, anteromedial temporal lobe areas, superior and medial temporal gyri, striatum, red nucleus, thalamus, precerebellar nuclei.Pattern II
Motor cortex, bulbar somatomotor neurons and the spinal cord anterior horn.Pattern III
Visual cortex.Pattern IV
TDP-43 (ALS)152 Agranular motor cortex, brainstem motor nuclei of cranial nerves V, VII and X–XII, and spinal cord a-motoneurons.Stage 1
Prefrontal neocortex (middle frontal gyrus), brainstem reticular formation, precerebellar nuclei and the red nucleus.Stage 2
Prefrontal (gyrus rectus and orbital gyri), and then postcentral neocortex and striatum.Stage 3
Anteromedial portions of the temporal lobe, including the hippocampus.Stage 4
TDP-43 (AD)154 Amygdala.Stage 1
Entorhinal cortex and subiculum.Stage 2
Dentate gyrus of the hippocampus and occipitotemporal cortex.Stage 3
Insular cortex, ventral striatum, basal forebrain and inferior temporal cortex.Stage 4
Substantia nigra, inferior olive and midbrain tectum.Stage 5
Basal ganglia and middle frontal cortex.Stage 6
aSyn (MSA-P)156 Striatum, lentiform nucleus, substantia nigra, brainstem white matter tracts, cerebellar subcortical white matter, motor cortex, mid-frontal cortex and sensory cortex.Phase 1
Spinal cord and thalamus.Phase 2
Hippocampus and amygdala.Phase 3
Visual cortex.Phase 4
aSyn (MSA-C)155 Cerebellum and cerebellar brainstem connectivities.Phase 1
Pyramidal and extrapyramidal white matter.Phase 2
Neocortex and basal ganglia grey matter.Phase 3
Amygdala and hippocampus.Phase 4
aSyn (Lewy)72 Dorsal IX/X motor nucleus and/or intermediate reticular zone (medulla oblongata).Stage 1
Caudal raphe nuclei, gigantocellular reticular nucleus, coeruleus–subcoeruleus complex (pons).Stage 2
Pars compacta of the substantia nigra (midbrain).Stage 3
Temporal mesocortex (transentorhinal region, amygdala) and allocortex (CA2-plexus).Stage 4
High-order sensory association areas of the neocortex and prefrontal neocortex.Stage 5
First-order sensory association areas of the neocortex and premotor areas, mild changes in primary sensory areas and the primary motor field.Stage 6
  • AD, Alzheimer’s disease; ALS, amyotrophic lateral sclerosis; C, cerebellar type; CA, Cornu Ammonis; MSA, multiple system atrophy; P, parkinsonian type; TDP-43, Transactive response (TAR) DNAbinding protein 43; aSyn, α-synuclein; bvFTD, behavioural variant of frontotemporal dementia.