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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.
GLOSSARY
- AD=
- Alzheimer disease;
- BMDB=
- brief mental deterioration battery;
- DLB=
- dementia with Lewy bodies;
- ENF=
- epidermal nerve fiber;
- FTD=
- frontotemporal dementia;
- IPD=
- idiopathic Parkinson disease;
- MIBG=
- iodine-123-meta-iodobenzylguanidine;
- MMSE=
- Mini-Mental State Examination;
- NSD=
- nonsynucleinopathy dementia;
- OH=
- orthostatic hypotension;
- p-syn=
- phosphorylated α-synuclein;
- PAF=
- pure autonomic failure;
- PGP=
- protein gene product;
- RBD=
- REM sleep behavior disorder;
- SFN=
- small fiber neuropathy;
- TH=
- tyrosine hydroxylase;
- UPDRS=
- Unified Parkinson's Disease Rating Scale;
- VaD=
- vascular dementia;
- VIP=
- vasoactive intestinal polypeptide
Footnotes
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Supplemental data at Neurology.org
Editorial, page 310
- Received September 14, 2016.
- Accepted in final form March 22, 2017.
- © 2017 American Academy of Neurology
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- Author response: How does this study differentiate among different synucleinopathies?
- How does this study differentiate among different synucleinopathies?
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