title: APOE ε4 increases risk for dementia in pure synucleinopathies.
abstract: OBJECTIVE
  To test for an association between the apolipoprotein E (APOE) ϵ4 allele and dementias with synucleinopathy.
  
  
  METHODS
  Genetic case-control association study.
  
  
  METHODS
  Academic research.
  
  
  METHODS
  Autopsied subjects were classified into 5 categories: dementia with high-level Alzheimer disease (AD) neuropathologic changes (NCs) but without Lewy body disease (LBD) NCs (AD group; n=244), dementia with LBDNCs and high-level ADNCs (LBD-AD group; n=224), dementia with LBDNCs and no or low levels of ADNCs (pure DLB [pDLB] group; n=91), Parkinson disease dementia (PDD) with no or low levels of ADNCs (n=81), and control group (n=269). MAIN OUTCOME MEASURE The APOE allele frequencies. RESULTS The APOE ϵ4 allele frequency was significantly higher in the AD (38.1%), LBD-AD (40.6%), pDLB (31.9%), and PDD (19.1%) groups compared with the control group (7.2%; overall χ(2)(4)=185.25; P=5.56 × 10(-39)), and it was higher in the pDLB group than the PDD group (P= .01). In an age-adjusted and sex-adjusted dominant model, ϵ4 was strongly associated with AD (odds ratio, 9.9; 95% CI, 6.4-15.3), LBD-AD (odds ratio, 12.6; 95% CI, 8.1-19.8), pDLB (odds ratio, 6.1; 95% CI, 3.5-10.5), and PDD (odds ratio, 3.1; 95% CI, 1.7-5.6). CONCLUSIONS The APOE ϵ4 allele is a strong risk factor across the LBD spectrum and occurs at an increased frequency in pDLB relative to PDD. This suggests that ϵ4 increases the likelihood of presenting with dementia in the context of a pure synucleinopathy. The elevated ϵ4 frequency in the pDLB and PDD groups, in which the overall brain neuritic plaque burden was low, indicates that apoE might contribute to neurodegeneration through mechanisms unrelated to amyloid processing.
authors: Veterans Affairs Puget Sound Health Care System, Seattle,WA98108, USA.
authors: Debby
authors: D
authors: Tsuang
authors: James B
authors: JB
authors: Leverenz
authors: Oscar L
authors: OL
authors: Lopez
authors: Ronald L
authors: RL
authors: Hamilton
authors: David A
authors: DA
authors: Bennett
authors: Julie A
authors: JA
authors: Schneider
authors: Aron S
authors: AS
authors: Buchman
authors: Eric B
authors: EB
authors: Larson
authors: Paul K
authors: PK
authors: Crane
authors: Jeffrey A
authors: JA
authors: Kaye
authors: Patricia
authors: P
authors: Kramer
authors: Randy
authors: R
authors: Woltjer
authors: John Q
authors: JQ
authors: Trojanowski
authors: Daniel
authors: D
authors: Weintraub
authors: Alice S
authors: AS
authors: Chen-Plotkin
authors: David J
authors: DJ
authors: Irwin
authors: Jacqueline
authors: J
authors: Rick
authors: Gerard D
authors: GD
authors: Schellenberg
authors: G Stennis
authors: GS
authors: Watson
authors: Walter
authors: W
authors: Kukull
authors: Peter T
authors: PT
authors: Nelson
authors: Gregory A
authors: GA
authors: Jicha
authors: Janna H
authors: JH
authors: Neltner
authors: Doug
authors: D
authors: Galasko
authors: Eliezer
authors: E
authors: Masliah
authors: Joseph F
authors: JF
authors: Quinn
authors: Kathryn A
authors: KA
authors: Chung
authors: Dora
authors: D
authors: Yearout
authors: Ignacio F
authors: IF
authors: Mata
authors: Jia Y
authors: JY
authors: Wan
authors: Karen L
authors: KL
authors: Edwards
authors: Thomas J
authors: TJ
authors: Montine
authors: Cyrus P
authors: CP
authors: Zabetian
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology; D053327:Apolipoprotein E4 / Q000235:genetics*; D016022:Case-Control Studies; D003704:Dementia / Q000235:genetics* / Q000473:pathology*; D005260:Female; D005787:Gene Frequency / Q000235:genetics*; D006801:Humans; D020961:Lewy Body Disease / Q000235:genetics / Q000473:pathology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics / Q000473:pathology; D012189:Retrospective Studies; D012307:Risk Factors; D051843:Synucleins / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D053327:Apolipoprotein E4; D051843:Synucleins