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. Author manuscript; available in PMC: 2021 Sep 29.
Published in final edited form as: Nat Med. 2017 Feb 7;23(2):1–13. doi: 10.1038/nm.4269

Table 1.

Summary of diseases associated with α-synuclein toxicity

Disease Genes associated Symptoms Pathology
Parkinson’s disease (PD)

  • Autosomal dominant (SNCA4–10,, LRRK2, VPS35, EIF4G1, DNAJC13, CHCHD2; SNCA duplication/triplication11,12)

  • Autosomal recessive (PARK2, PINK1 and DJ-1)

  • Parkinsonism (bradykinesia, muscular rigidity, resting tremors and postural instability)24

  • Nonmotor symptoms (constipation, impaired olfaction and rapid-eye movement sleep behavior disorder (RBD))

  • Cognitive impairment

  • SNc dopaminergic degeneration24

  • Variable neuron loss in areas including locus coeruleus (LC), dorsal motor nucleus of the vagus (DMV) and the olfactory bulb123

  • α-synuclein Lewy body and neurite pathology in neurons1
Parkinson’s disease with dementia (PDD) or dementia with Lewy bodies (DLB) N/A

  • Parkinsonism and dementia34

  • In DLB versus PDD: fewer resting tremors, bilateral parkinsonism

  • Cholinergic/SNc dopaminergic degeneration34

  • α-synuclein Lewy body and neurite pathology in neurons17

  • aβ amyloid plaques and tau tangles
Multiple system atrophy (MSA)

  • Autosomal dominant (SHC2 copy-number loss, SNCA)

  • Autosomal recessive (COQ2)

  • Parkinsonism, cerebellar ataxia, autonomic failure33

  • Nonmotor symptoms (sexual dysfunction, urinary incontinence and RBD)

  • SNc/olivopontocerebellar degeneration33

  • α-synuclein pathology in oligodendrocytes16
Gaucher’s disease (GD)

  • Autosomal recessive (GBA1)

  • Type I adult-onset (thrombocytopenia, anemia, hepatosplenomegaly and bone pain)37

  • Type II (infant)/III (juvenile) neuropathic form (seizures, cognitive impairment and oculomotor problems)

  • α-synuclein Lewy body and neurite pathology in some patients37
Additional lysosomal storage disorders (LSDs)

  • Sanfilippo syndrome (SGSH, NAGLU)

  • Tay–Sachs and Sandhoff diseases (HEXA/HEXB)

  • Hunter’s syndrome (I2S)

  • Niemann–Pick type C (NPC1/2)

  • Multisystem disorder18

  • α-synuclein Lewy body and neurite pathology in some patients18
Neurodegeneration with brain iron accumulation (NBIA)

  • Autosomal recessive (C19orf12, PLA2G6, ATP13A2/PARK9)

  • Variable symptoms that may include dystonia, muscle rigidity, spasticity and ataxia39

  • Iron accumulation in the globus pallidus and SNc39

  • α-synuclein Lewy body and neurite pathology in some patients
Alzheimer’s disease (AD)

  • Autosomal dominant (APP, PS1/2)

  • Progressive memory loss35

  • Cognitive impairment

  • Cortical and CA1 hippocampal degeneration35

  • aβ amyloid plaques and tau tangles

  • α-synuclein Lewy body and neurite pathology in some patients