PMID- 36396603
OWN - NLM
STAT- MEDLINE
DCOM- 20230531
LR  - 20240502
IS  - 1552-5279 (Electronic)
IS  - 1552-5260 (Print)
IS  - 1552-5260 (Linking)
VI  - 19
IP  - 5
DP  - 2023 May
TI  - Blood levels of MCP-1 modulate the genetic risks of Alzheimer's disease mediated 
      by HLA-DRB1 and APOE for Alzheimer's disease.
PG  - 1925-1937
LID - 10.1002/alz.12851 [doi]
AB  - INTRODUCTION: C-Reactive protein (CRP) and monocyte chemoattractant protein-1 
      (MCP-1) are both implicated in the peripheral proinflammatory cascade and 
      blood-brain barrier (BBB) disruption. Since the blood CRP level increases 
      Alzheimer's disease (AD) risk depending on the apolipoprotein E (APOE) genotype, 
      we hypothesized that the blood MCP-1 level exerts different effects on the AD 
      risk depending on the genotypes. METHODS: Using multiple regression analyses, 
      data from the Framingham Heart Study (n = 2884) and Alzheimer's Disease 
      Neuroimaging Initiative study (n = 231) were analyzed. RESULTS: An elevated blood 
      MCP-1 level was associated with AD risk in major histocompatibility complex, 
      Class II, DR beta 1 (HLA-DRB1) rs9271192-AC/CC (hazard ratio [HR] = 3.07, 95% 
      confidence interval [CI] = 1.50-6.28, p = 0.002) and in APOE epsilon4 carriers (HR = 
      3.22, 95% CI = 1.59-6.53, p = 0.001). In contrast, among HLA-DRB1 rs9271192-AA 
      and APOE epsilon4 noncarriers, blood MCP-1 levels were not associated with these 
      phenotypes. DISCUSSION: Since HLA-DRB1 and APOE are expressed in the BBB, blood 
      MCP-1 released in the peripheral inflammatory cascade may function as a mediator 
      of the effects of HLA-DRB1 rs9271192-AC/CC and APOE epsilon4 genotypes on AD 
      pathogenesis in the brain via the BBB pathways.
CI  - (c) 2022 the Alzheimer's Association.
FAU - Huang, Jinghan
AU  - Huang J
AUID- ORCID: 0000-0003-0628-6022
AD  - Department of Medicine (Biomedical Genetics), Boston University School of 
      Medicine, Boston, Massachusetts, USA.
FAU - Stein, Thor D
AU  - Stein TD
AD  - Department of Pathology and Laboratory Medicine, Boston University School of 
      Medicine, Boston, Massachusetts, USA.
AD  - Alzheimer's Disease Research Center, Boston University School of Medicine, 
      Boston, Massachusetts, USA.
AD  - VA Boston Healthcare System, Boston, Massachusetts, USA.
FAU - Wang, Yixuan
AU  - Wang Y
AD  - Department of Medicine (Biomedical Genetics), Boston University School of 
      Medicine, Boston, Massachusetts, USA.
FAU - Ang, Ting Fang Alvin
AU  - Ang TFA
AD  - Department of Anatomy & Neurobiology, Boston University School of Medicine, 
      Boston, Massachusetts, USA.
AD  - Department of Epidemiology, Boston University School of Public Health, Boston, 
      Massachusetts, USA.
FAU - Tao, Qiushan
AU  - Tao Q
AD  - Department of Pharmacology & Experimental Therapeutics, Boston University School 
      of Medicine, Boston, Massachusetts, USA.
FAU - Lunetta, Kathryn L
AU  - Lunetta KL
AD  - Departments of Biostatistics, Boston University School of Public Health, Boston, 
      Massachusetts, USA.
FAU - Massaro, Joseph
AU  - Massaro J
AD  - Departments of Biostatistics, Boston University School of Public Health, Boston, 
      Massachusetts, USA.
AD  - Framingham Heart Study, Boston University School of Medicine, Framingham, 
      Massachusetts, USA.
FAU - Akhter-Khan, Samia C
AU  - Akhter-Khan SC
AD  - Framingham Heart Study, Boston University School of Medicine, Framingham, 
      Massachusetts, USA.
AD  - Department of Health Service & Population Research, Institute of Psychiatry, 
      Psychology & Neuroscience, King's College London, London, UK.
FAU - Mez, Jesse
AU  - Mez J
AD  - Alzheimer's Disease Research Center, Boston University School of Medicine, 
      Boston, Massachusetts, USA.
AD  - Framingham Heart Study, Boston University School of Medicine, Framingham, 
      Massachusetts, USA.
AD  - Department of Neurology, Boston University School of Medicine, Boston, 
      Massachusetts, USA.
FAU - Au, Rhoda
AU  - Au R
AD  - Alzheimer's Disease Research Center, Boston University School of Medicine, 
      Boston, Massachusetts, USA.
AD  - Department of Anatomy & Neurobiology, Boston University School of Medicine, 
      Boston, Massachusetts, USA.
AD  - Department of Epidemiology, Boston University School of Public Health, Boston, 
      Massachusetts, USA.
AD  - Framingham Heart Study, Boston University School of Medicine, Framingham, 
      Massachusetts, USA.
AD  - Department of Neurology, Boston University School of Medicine, Boston, 
      Massachusetts, USA.
FAU - Farrer, Lindsay A
AU  - Farrer LA
AD  - Department of Medicine (Biomedical Genetics), Boston University School of 
      Medicine, Boston, Massachusetts, USA.
AD  - Alzheimer's Disease Research Center, Boston University School of Medicine, 
      Boston, Massachusetts, USA.
AD  - Department of Epidemiology, Boston University School of Public Health, Boston, 
      Massachusetts, USA.
AD  - Departments of Biostatistics, Boston University School of Public Health, Boston, 
      Massachusetts, USA.
AD  - Framingham Heart Study, Boston University School of Medicine, Framingham, 
      Massachusetts, USA.
AD  - Department of Neurology, Boston University School of Medicine, Boston, 
      Massachusetts, USA.
AD  - Department of Ophthalmology, Boston University School of Medicine, Boston, 
      Massachusetts, USA.
FAU - Zhang, Xiaoling
AU  - Zhang X
AD  - Department of Medicine (Biomedical Genetics), Boston University School of 
      Medicine, Boston, Massachusetts, USA.
AD  - Departments of Biostatistics, Boston University School of Public Health, Boston, 
      Massachusetts, USA.
FAU - Qiu, Wei Qiao
AU  - Qiu WQ
AD  - Alzheimer's Disease Research Center, Boston University School of Medicine, 
      Boston, Massachusetts, USA.
AD  - Department of Pharmacology & Experimental Therapeutics, Boston University School 
      of Medicine, Boston, Massachusetts, USA.
AD  - Department of Psychiatry, Boston University School of Medicine, Boston, 
      Massachusetts, USA.
CN  - Alzheimer's Disease Neuroimaging Initiative
AD  - Department of Medicine (Biomedical Genetics), Boston University School of 
      Medicine, Boston, Massachusetts, USA.
LA  - eng
GR  - U01 AG024904/AG/NIA NIH HHS/United States
GR  - R01 AG059424/AG/NIA NIH HHS/United States
GR  - R01 AG048927/AG/NIA NIH HHS/United States
GR  - RF1 AG057519/AG/NIA NIH HHS/United States
GR  - U19 AG068753/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20221117
PL  - United States
TA  - Alzheimers Dement
JT  - Alzheimer's & dementia : the journal of the Alzheimer's Association
JID - 101231978
RN  - 0 (Apolipoprotein E4)
RN  - 0 (Apolipoproteins E)
RN  - 0 (Chemokine CCL2)
RN  - 0 (HLA-DRB1 Chains)
SB  - IM
MH  - Humans
MH  - *Alzheimer Disease/blood/genetics
MH  - Apolipoprotein E4/genetics
MH  - *Apolipoproteins E/genetics
MH  - *Chemokine CCL2/blood
MH  - Genotype
MH  - *HLA-DRB1 Chains/genetics
PMC - PMC10182187
MID - NIHMS1843358
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - MCP-1
OT  - blood
OT  - genotypes
EDAT- 2022/11/18 06:00
MHDA- 2023/05/15 06:42
PMCR- 2024/05/01
CRDT- 2022/11/17 22:23
PHST- 2022/09/13 00:00 [revised]
PHST- 2022/07/26 00:00 [received]
PHST- 2022/10/05 00:00 [accepted]
PHST- 2023/05/15 06:42 [medline]
PHST- 2022/11/18 06:00 [pubmed]
PHST- 2022/11/17 22:23 [entrez]
PHST- 2024/05/01 00:00 [pmc-release]
AID - 10.1002/alz.12851 [doi]
PST - ppublish
SO  - Alzheimers Dement. 2023 May;19(5):1925-1937. doi: 10.1002/alz.12851. Epub 2022 
      Nov 17.