Vincenzo Donadio1, Alex Incensi2, Giovanni Rizzo2, Sabina Capellari2, Roberta Pantieri2, Michelangelo Stanzani Maserati2, Grazia Devigili2, Roberto Eleopra2, Giovanni Defazio2, Federico Montini2, Agostino Baruzzi2, Rocco Liguori2. 1. From the IRCCS Institute of Neurological Sciences (V.D., A.I., G.R., S.C., R.P., M.S.M., F.M., A.B., R.L.); Department of Biomedical and Neuromotor Sciences (G.R., S.C., R.L.), University of Bologna; Neurological Unit (G. Devigili, R.E.), Department of Neurosciences, "Santa Maria della Misericordia" University Hospital Udine; and Department of Basic Medical Sciences (G. Defazio), Neuroscience and Sense Organs, "Aldo Moro" University of Bari, Italy. vincenzo.donadio@unibo.it. 2. From the IRCCS Institute of Neurological Sciences (V.D., A.I., G.R., S.C., R.P., M.S.M., F.M., A.B., R.L.); Department of Biomedical and Neuromotor Sciences (G.R., S.C., R.L.), University of Bologna; Neurological Unit (G. Devigili, R.E.), Department of Neurosciences, "Santa Maria della Misericordia" University Hospital Udine; and Department of Basic Medical Sciences (G. Defazio), Neuroscience and Sense Organs, "Aldo Moro" University of Bari, Italy.
Abstract
OBJECTIVE: To investigate whether (1) phosphorylated α-synuclein (p-syn) deposits in skin nerves could be useful in differentiating dementia with Lewy bodies (DLB) from different forms of dementia and (2) small fiber neuropathy (SFN) is associated with DLB. METHODS: We studied 18 well-characterized patients with DLB (11 with autonomic dysfunction), 23 patients with nonsynucleinopathy dementia (NSD; 13 with young-onset Alzheimer disease dementia, 6 frontotemporal dementia, and 4 vascular dementia), and 25 healthy controls. All participants underwent skin biopsies from proximal (i.e., cervical) and distal (i.e., thigh and distal leg) sites to study small nerve fibers and deposits of p-syn, considered the pathologic form of α-synuclein. RESULTS: No p-syn was detected in any skin sample in patients with NSD and controls but was found in all patients with DLB. SFN was found in patients with DLB and the autonomic denervation of skin was more severe in patients with autonomic dysfunctions. CONCLUSIONS: (1) In autonomic skin nerves, p-syn is a sensitive biomarker for DLB diagnosis, helping to differentiate DLB from other forms of dementia, although this needs to be confirmed in a larger, more representative sample; and (2) skin autonomic neuropathy is part of the DLB pathology and may contribute to autonomic symptoms. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that p-syn in skin nerve fibers on skin biopsy accurately distinguishes DLB from other forms of dementia.
OBJECTIVE: To investigate whether (1) phosphorylated α-synuclein (p-syn) deposits in skin nerves could be useful in differentiating dementia with Lewy bodies (DLB) from different forms of dementia and (2) small fiber neuropathy (SFN) is associated with DLB. METHODS: We studied 18 well-characterized patients with DLB (11 with autonomic dysfunction), 23 patients with nonsynucleinopathy dementia (NSD; 13 with young-onset Alzheimer disease dementia, 6 frontotemporal dementia, and 4 vascular dementia), and 25 healthy controls. All participants underwent skin biopsies from proximal (i.e., cervical) and distal (i.e., thigh and distal leg) sites to study small nerve fibers and deposits of p-syn, considered the pathologic form of α-synuclein. RESULTS: No p-syn was detected in any skin sample in patients with NSD and controls but was found in all patients with DLB. SFN was found in patients with DLB and the autonomic denervation of skin was more severe in patients with autonomic dysfunctions. CONCLUSIONS: (1) In autonomic skin nerves, p-syn is a sensitive biomarker for DLB diagnosis, helping to differentiate DLB from other forms of dementia, although this needs to be confirmed in a larger, more representative sample; and (2) skin autonomic neuropathy is part of the DLB pathology and may contribute to autonomic symptoms. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that p-syn in skin nerve fibers on skin biopsy accurately distinguishes DLB from other forms of dementia.
Authors: Mitchell G Miglis; Jennifer Zitser; Logan Schneider; Emmanuel During; Safwan Jaradeh; Roy Freeman; Christopher H Gibbons Journal: Sleep Date: 2021-12-10 Impact factor: 6.313