Table 1.

Main neuropathological features of the different parkinsonisms.

Location	Type of Pathology	Macroscopic Localisation	Microscopic Changes	Localisation	Spreading
Parkinson Disease
CNS	LB and LN	SN, LC	Neuronal loss of neurons	Dopaminergic neurons of SN; neuronal loss of noradrenergic neurons in the LC, neuronal cell bodies—synapses, axons and astroglial cells [16,17,18]	Early: dorsal motor nucleus of the vagus and the anterior olfactory nucleus Medium: LC and SN Later: basal forebrain, amygdala, medial temporal lobe structures, and cortical areas
PNS	α-synuclein aggregates [19], phosphorylated α-synuclein inclusions [20]	Enteric, pelvic and cardiac ganglia [21,22,23,24,25,26,27] skin [28], pharyngeal motor and sensory branch of the vagus nerve, glossopharyngeal nerve, internal superior laryngeal nerve [29,30]	Axonal degeneration after traumatic nerve injury [31] small fibre neuropathy [32]	The spinous cell layer, pilosebaceous unit and eccrine glands [28], sympathetic ganglia and intermediolateral column of the medulla [27], distal cardiac sympathetic axons [25] gastrointestinal tract: 90% as neurites, 10% soma [33,34,35]	Peripheral-to-central spreading pattern of in sympathetic nervous system [36], rostro-caudal gradient in gastro-intestinal tract [37], spreading from vagal terminals of the gut to dorsal motor nucleus of vagus nerve [38,39]
Dementia with Lewy Bodies
CNS	LB, LN, α-synuclein aggregates in oligodendrocytes [40,41]	Diffuse neocortical, limbic, brainstem, amygdala, olfactory bulb, SN [42]	Neuronal loss of neurons	Diffuse neocortical, limbic, brainstem, amygdala, olfactory bulb, SN [42]	Due to Braak stages
Progressive Supranuclear Palsy
CNS	Accumulation of tau inclusions in neurons	Marked atrophy of the midbrain and superior cerebellar peduncle along with mild frontal cortical atrophy; STN smaller than normal	Inclusion bodies in astrocytes and in oligodendroglia	GP, STN, midbrain tectum, periaqueductal gray, LC, cerebellar dentate nucleus, corpus striatum, ventrolateral thalamus, red nucleus, pontine and medullary tegmentum, pontine base, inferior olivary nucleus	Due to Braak stages
Corticobasal Degeneration
CNS	Deposition of tau in neurons and glia [10,11,12,13,43]	Disproportionately more in forebrain structures, than in hindbrain	Pretangles, NFT, neuropil threads, astrocytic plaques, oligodendroglial coiled bodies [10,43]	Forebrain structures > hindbrain	Due to Braak stages
Multiple System Atrophy
CNS	α-synuclein inclusions [44]	Striatonigral degeneration and olivoponto-cerebellar atrophy	Accumulation of α-synuclein within GCIs, neuronal cytoplasmic inclusions [45,46]	Oligodendroglial cells, neurons [47,48]
PNS	Filamentous α-synuclein aggregates [49]	Multidomain autonomic nervous system failure [50,51,52], reduction of sensory afferent and postganglionic sympathetic fibres [53]	Cholinergic, catecholaminergic, noradrenergic, serotonergic preganglionic, postganglionic neurons [54,55,56,57], postganglionic fibres [58]	Cholinergic neurons in dorsal motor nucleus and ventrolateral nucleus ambiguous of the vagus [55], catecholaminergic neurons of ventrolateral medulla [54], medullary arcuate nucleus [59], noradrenergic LC [56], medullary serotonergic groups, ventrolateral medulla [60,61], ventromedullary NK-1-receptor-immunoreactive neurons [62], A5 noradrenergic neurons [57], caudal raphe nucleus with sparing of rostral raphe neurons [63,64], Edinger-Westphal nucleus and posterior hypothalamus [65], suprachiasmatic nucleus [66], pontomedullary reticular formation [46,67] sympathetic preganglionic neurons in intermediolateral column of thoracolumbar spinal cord [56,68], postganglionic sudomotor nerves [69], cardiac postganglionic sympathetic fibres [58], Schwann cells’ cytoplasm [49]

CNS—central nervous system; PNS—peripheral nervous system; LB—Lewy bodies; LN—Lewy neurites; SN—substantia nigra; LC—locus ceruleus; GCIs—glial cytoplasmic inclusions; STN—subthalamic nucleus; NfT—neurofibrillary tangles; GP—globus pallidus.