Familial Diffuse Lewy Body Disease, Eye Movement Abnormalities, and Distribution of Pathology

Abstract

Familial DLBD (not shown to be genetically as distinct from environmentally transmitted) has been shown to exist in an Irish family. Caution should be enjoined in the interpretation of defects in vertical gaze in the differential diagnosis of the parkinsonian syndromes.

Roles for the ubiquitin–proteasome pathway in protein quality control and signaling in the retina: Implications in the pathogenesis of age-related macular degeneration

“…Lewy bodies are ubiquitin-containing inclusions in many premature neurological aging syndromes. Studies show that α-synuclein, a neuron specific molecule of unknown functions is a substrate for the UPP and is found within neurofibrilary deposits in brains of patients with Parkinson-dementia and abnormal eye function [333]. This corroborates the concept that limited UPP activity is causally related to the “amyloid diseases”.…”

Roles for the ubiquitin–proteasome pathway in protein quality control and signaling in the retina: Implications in the pathogenesis of age-related macular degeneration

“…Lewy bodies are ubiquitin-containing inclusions in many premature neurological aging syndromes. Studies show that α-synuclein, a neuron specific molecule of unknown functions is a substrate for the UPP and is found within neurofibrilary deposits in brains of patients with Parkinson-dementia and abnormal eye function [333]. This corroborates the concept that limited UPP activity is causally related to the “amyloid diseases”.…”

Abnormal sleep architecture is an early feature in the E46K familial synucleinopathy

“…A primary sleep loss similar to that observed in the E46K family has not been documented previously in patients suffering a familial Lewy body disease either with or without a known genetic basis 25–33. It could be speculated that an early loss of physiological sleep rhythms is a peculiar phenotype of the E46K mutation.…”

Recognizing Atypical Parkinsonisms: “Red Flags” and Therapeutic Approaches

“…Vertical gaze impairment in general is often associated with PSP, but this is nonspecific and can be seen in other neurodegenerative disorders and normal aging. 17 By contrast, downgaze impairment is the most sensitive predictor for PSP, though both upgaze and horizontal ophthalmoparesis can progressively develop as well. Supranuclear gaze palsy can be overcome by changes in head position or oculocephalic maneuvers, but testing is often limited by axial rigidity.…”

Roles for the ubiquitin–proteasome pathway in protein quality control and signaling in the retina: Implications in the pathogenesis of age-related macular degeneration

“…Lewy bodies are ubiquitin-containing inclusions in many premature neurological aging syndromes. Studies show that α-synuclein, a neuron specific molecule of unknown functions is a substrate for the UPP and is found within neurofibrilary deposits in brains of patients with Parkinson-dementia and abnormal eye function [333]. This corroborates the concept that limited UPP activity is causally related to the “amyloid diseases”.…”

Abnormal sleep architecture is an early feature in the E46K familial synucleinopathy

“…A primary sleep loss similar to that observed in the E46K family has not been documented previously in patients suffering a familial Lewy body disease either with or without a known genetic basis 25–33. It could be speculated that an early loss of physiological sleep rhythms is a peculiar phenotype of the E46K mutation.…”

Recognizing Atypical Parkinsonisms: “Red Flags” and Therapeutic Approaches

“…Vertical gaze impairment in general is often associated with PSP, but this is nonspecific and can be seen in other neurodegenerative disorders and normal aging. 17 By contrast, downgaze impairment is the most sensitive predictor for PSP, though both upgaze and horizontal ophthalmoparesis can progressively develop as well. Supranuclear gaze palsy can be overcome by changes in head position or oculocephalic maneuvers, but testing is often limited by axial rigidity.…”

Roles for the ubiquitin–proteasome pathway in protein quality control and signaling in the retina: Implications in the pathogenesis of age-related macular degeneration

“…Lewy bodies are ubiquitin-containing inclusions in many premature neurological aging syndromes. Studies show that α-synuclein, a neuron specific molecule of unknown functions is a substrate for the UPP and is found within neurofibrilary deposits in brains of patients with Parkinson-dementia and abnormal eye function [333]. This corroborates the concept that limited UPP activity is causally related to the “amyloid diseases”.…”

Abnormal sleep architecture is an early feature in the E46K familial synucleinopathy

“…A primary sleep loss similar to that observed in the E46K family has not been documented previously in patients suffering a familial Lewy body disease either with or without a known genetic basis 25–33. It could be speculated that an early loss of physiological sleep rhythms is a peculiar phenotype of the E46K mutation.…”

Recognizing Atypical Parkinsonisms: “Red Flags” and Therapeutic Approaches

“…Vertical gaze impairment in general is often associated with PSP, but this is nonspecific and can be seen in other neurodegenerative disorders and normal aging. 17 By contrast, downgaze impairment is the most sensitive predictor for PSP, though both upgaze and horizontal ophthalmoparesis can progressively develop as well. Supranuclear gaze palsy can be overcome by changes in head position or oculocephalic maneuvers, but testing is often limited by axial rigidity.…”