The dementia-associated APOE ε4 allele is not associated with rapid eye movement sleep behavior disorder

Abstract

The dementia-associated APOE ε4 allele is not associated with REM sleep behavior disorder, Neurobiology of Aging (2016Aging ( ), doi: 10.1016Aging ( /j.neurobiolaging.2016 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPTAbstract: The current study aimed to examine whether the APOE ε4 allele, associated with dementia with Lewy bodies (DLB), and possibly with dementia in Parkinson's disease (PD), is also associated with idiopathic REM sleep behavior disorder (RBD). Two SNPs, rs429358 and rs7412, were genotyped in RBD patients (n=480) and in controls (n=823). APOE ε4 allele frequency was 0.14 among RBD patients and 0.13 among controls (OR=1.11, 95% CI 0.88-1.40, p=0.41). APOE ε4 allele frequencies were similar in those who converted to DLB (0.14) and those who converted to PD (0.12) or multiple system atrophy (0.14, p=1.0). The APOE ε4 allele is neither a risk factor for RBD nor it is associated with conversion from RBD to DLB or other synucleinopathies.

Fine‐Mapping of SNCA in Rapid Eye Movement Sleep Behavior Disorder and Overt Synucleinopathies

“…Previous genetic findings also supported an only partially overlapping genetic background between iRBD, PD, and DLB . Although GBA variants, implicated in both PD and DLB, were also strongly associated with RBD, the PD‐causing LRRK2 mutations and the DLB‐associated APOE ε4 allele were not associated with RBD . The H1/H2 MAPT haplotypes, associated with PD and other neurodegenerative disorders, were not associated with RBD either .…”

“…15 However, no association has been found with other key PD or DLB risk variants in LRRK2, 16 MAPT haplotypes, 17 and the APOE ε4 risk haplotype. 18 Thus far, the role of the SNCA gene in iRBD has not been thoroughly studied. SNCA encodes α-synuclein, the main protein component of Lewy bodies and neurites in synucleinopathies.…”

Genetic, Structural, and Functional Evidence Link TMEM175 to Synucleinopathies

“…Previous genetic studies in idiopathic RBD suggested that whereas some of the genes that are associated with PD and DLB, such as GBA and the protective LRRK2 haplotype, are also associated with RBD, other genes such as MAPT and APOE are not. The current findings demonstrating that the TMEM175 p.M393T variant is also associated with RBD add to our understanding of the genetic background of RBD.…”

Multiple system atrophy and apolipoprotein E

“…15 It also is worth noting that in agreement with these findings, a recent study reported no association between rapid eye movement sleep behavior disorder (which could be a clinical prodromal feature preceding the development of MSA) and risk of MSA. 16 …”