title: The Threshold Theory for Parkinson's Disease.
abstract: Parkinson's disease (PD) is recognized by the accumulation of α-synuclein within neurons. In contrast to the current ascending theory where α-synuclein would propagate from neuron to neuron, we now propose the threshold theory for PD based on evidence of parallel degeneration of both central nervous system (CNS) and peripheral nervous system (PNS) in PD. The functional threshold is lower for the emergence of early symptoms before the classical motor symptoms of PD. This is due to the larger functional reserve of the midbrain dopamine and integrated basal ganglia motor systems to control movement. This threshold theory better accounts for the current neurobiology of PD symptom progression compared to the hypothesis that the disease ascends from the PNS to the CNS as proposed by Braak's hypothesis.
authors.affiliation: Department of Biochemistry, Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa 31096, Israel. Electronic address: simone@tx.technion.ac.il.
authors.forename: Simone
authors.initials: S
authors.lastname: Engelender
authors.affiliation: Neuroregeneration Research Institute, McLean Hospital, Belmont, MA 02478, USA; Harvard Medical School, Boston, MA 02115, USA. Electronic address: isacson@hms.harvard.edu.
authors.forename: Ole
authors.initials: O
authors.lastname: Isacson
mesh_terms: D000818:Animals; D001921:Brain / Q000503:physiopathology; D059290:Dopaminergic Neurons / Q000502:physiology; D006801:Humans; D008959:Models, Neurological; D010300:Parkinson Disease / Q000503:physiopathology*
keywords: Parkinson's disease; dopaminergic neurons; functional threshold; spreading theory; α-synuclein