alpha-synuclein and Sleep-Apnea-Syndromes

Topics: alpha-Synuclein; Humans; Parkinson Disease; Sleep Apnea Syndromes; Sleep Apnea, Obstructive

Respiratory dysfunction, including sleep disordered breathing, is characteristic of multiple system atrophy (MSA) and may reflect degeneration of brainstem respiratory nuclei involved in respiratory rhythmogenesis and chemosensitivity, including the pre-Bötzinger complex (preBötC), nucleus raphe pallidus (RPa), and nucleus raphe obscurus (ROb). However, impaired ventilatory responses to hypercapnia have also been reported in dementia with Lewy bodies (DLB), suggesting that these nuclei may also be affected in DLB.. To determine whether there is involvement of the preBötC, RPa, and ROb in DLB.. We applied stereological methods to analyze sections immunostained for neurokinin-1 receptor and tryptophan hydroxylase in neuropathologically confirmed cases of DLB, MSA, and controls.. Reduction of neuronal density occurred in all three nuclei in DLB, as well as in MSA. The magnitude of neuronal depletion in ROb was similar in DLB and MSA (49% versus 56% respectively, compared to controls, P < 0.05), but neuronal loss in the preBötC and RPa was less severe in DLB than in MSA (40% loss in preBötC of DLB, P < 0.05 and 68% loss in MSA, P < 0.0001, compared to controls; 46% loss in RPa of DLB, P < 0.05 and 73% loss in MSA P < 0.0001, compared to controls).. Medullary respiratory nuclei are affected in dementia with Lewy bodies but less severely than in multiple system atrophy. This may help explain differences in the frequency of sleep disordered breathing in these two disorders.

Topics: Aged, 80 and over; alpha-Synuclein; Case-Control Studies; Female; Humans; Lewy Body Disease; Male; Medulla Oblongata; Middle Aged; Multiple System Atrophy; Neurons; Receptors, Neurokinin-1; Sleep Apnea Syndromes; Tryptophan Hydroxylase

Topics: Aged; alpha-Synuclein; Atrophy; Brain; Cognition Disorders; Depressive Disorder; Diagnosis, Differential; Disease Progression; Electroencephalography; Fatal Outcome; Gait Disorders, Neurologic; Genetic Markers; Genetic Predisposition to Disease; Humans; Lewy Body Disease; Magnetic Resonance Imaging; Male; Memory Disorders; Psychotic Disorders; REM Sleep Behavior Disorder; Sleep Apnea Syndromes; Urination Disorders

The human arcuate nucleus (ArcN) has been considered akin to the pontine precerebellar nuclei. However, there is anatomical, functional, and clinical evidence that the ArcN may be the homologue of chemosensitive areas of the ventral medullary surface involved in ventilatory responses to hypercarbia and cerebrospinal fluid acidosis. Acetylcholine has been involved in mechanisms of central chemosensitivity. Loss of ArcN neurons has been reported in patients with multiple system atrophy (MSA), a disorder characterized by disturbed automatic ventilation, but the neurochemical identity of these neurons is undetermined. We sought to determine whether the ArcN contains cholinergic neurons and whether these neurons are depleted in patients with MSA. Medullae were obtained from six patients with MSA, five patients with Parkinson's disease (PD) and six sex- and age-matched controls. Fifty-micron transverse sections obtained through the mid-olivary levels were processed for acetylcholinesterase (AchE), choline acetyltransferase (CAT), and alpha-synuclein immunoreactivity. We found that the ArcN contained CAT-positive neurons. There was a significant decrease in density of cholinergic ArcN neurons in MSA but not in PD patients. alpha-Synuclein-containing inclusions were present in the ArcN of MSA patients. Depletion of cholinergic neurons may provide a substrate for disturbances in automatic respiration in MSA patients.

Topics: Aged; Aged, 80 and over; alpha-Synuclein; Arcuate Nucleus of Hypothalamus; Choline O-Acetyltransferase; Cholinergic Fibers; Female; Humans; Inclusion Bodies; Male; Middle Aged; Multiple System Atrophy; Nerve Tissue Proteins; Neurons; Sleep Apnea Syndromes; Synucleins