PMID- 32943069
OWN - NLM
STAT- MEDLINE
DCOM- 20210721
LR  - 20210724
IS  - 1742-2094 (Electronic)
IS  - 1742-2094 (Linking)
VI  - 17
IP  - 1
DP  - 2020 Sep 17
TI  - Microglial-associated responses to comorbid amyloid pathology and 
      hyperhomocysteinemia in an aged knock-in mouse model of Alzheimer's disease.
PG  - 274
LID - 10.1186/s12974-020-01938-7 [doi]
LID - 274
AB  - BACKGROUND: Elevated blood homocysteine levels, termed hyperhomocysteinemia 
      (HHcy), is a prevalent risk factor for Alzheimer's disease (AD) in elderly 
      populations. While dietary supplementation of B-vitamins is a generally effective 
      method to lower homocysteine levels, there is little if any benefit to cognition. 
      In the context of amyloid pathology, dietary-induced HHcy is known to enhance 
      amyloid deposition and certain inflammatory responses. Little is known, however, 
      about whether there is a more specific effect on microglia resulting from 
      combined amyloid and HHcy pathologies. METHODS: The present study used a knock-in 
      mouse model of amyloidosis, aged to 12 months, given 8 weeks of B-vitamin 
      deficiency-induced HHcy to better understand how microglia are affected in this 
      comorbidity context. RESULTS: We found that HHcy-inducing diet increased amyloid 
      plaque burden, altered the neuroinflammatory milieu, and upregulated the 
      expression of multiple damage-associated and "homeostatic" microglial genes. 
      CONCLUSIONS: Taken together, these data indicate complex effects of comorbid 
      pathologies on microglial function that are not driven solely by increased 
      amyloid burden. Given the highly dynamic nature of microglia, their central role 
      in AD pathology, and the frequent occurrence of various comorbidities in AD 
      patients, it is increasingly important to understand how microglia respond to 
      mixed pathological processes.
FAU - Braun, David J
AU  - Braun DJ
AD  - Sanders-Brown Center on Aging, University of Kentucky, 101 Sanders-Brown Bldg., 
      800 S. Limestone Street, Lexington, KY, 40536, USA. david.braun1@uky.edu.
FAU - Dimayuga, Edgardo
AU  - Dimayuga E
AD  - Sanders-Brown Center on Aging, University of Kentucky, 101 Sanders-Brown Bldg., 
      800 S. Limestone Street, Lexington, KY, 40536, USA.
FAU - Morganti, Josh M
AU  - Morganti JM
AD  - Sanders-Brown Center on Aging, University of Kentucky, 101 Sanders-Brown Bldg., 
      800 S. Limestone Street, Lexington, KY, 40536, USA.
AD  - Department of Neuroscience, University of Kentucky, Lexington, KY, USA.
AD  - Spinal Cord and Brain Injury Research Center, University of Kentucky, Lexington, 
      KY, USA.
FAU - Van Eldik, Linda J
AU  - Van Eldik LJ
AUID- ORCID: 0000-0002-8139-6400
AD  - Sanders-Brown Center on Aging, University of Kentucky, 101 Sanders-Brown Bldg., 
      800 S. Limestone Street, Lexington, KY, 40536, USA. linda.vaneldik@uky.edu.
AD  - Department of Neuroscience, University of Kentucky, Lexington, KY, USA. 
      linda.vaneldik@uky.edu.
AD  - Spinal Cord and Brain Injury Research Center, University of Kentucky, Lexington, 
      KY, USA. linda.vaneldik@uky.edu.
LA  - eng
GR  - F32 AG058456/AG/NIA NIH HHS/United States
GR  - RF1 AG064859/AG/NIA NIH HHS/United States
GR  - F32AG058456/AG/NIA NIH HHS/United States
GR  - RF1AG064859/AG/NIA NIH HHS/United States
PT  - Journal Article
DEP - 20200917
PL  - England
TA  - J Neuroinflammation
JT  - Journal of neuroinflammation
JID - 101222974
SB  - IM
MH  - Aging/genetics/*metabolism/pathology
MH  - Alzheimer Disease/genetics/*metabolism/pathology
MH  - Animals
MH  - Cerebral Cortex/metabolism/pathology
MH  - Disease Models, Animal
MH  - Gene Knock-In Techniques/*methods
MH  - Hippocampus/metabolism/pathology
MH  - Hyperhomocysteinemia/genetics/*metabolism/pathology
MH  - Mice
MH  - Mice, Transgenic
MH  - Microglia/*metabolism/pathology
MH  - Plaque, Amyloid/genetics/*metabolism/pathology
PMC - PMC7499995
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - Amyloid
OT  - Homocysteine
OT  - Hyperhomocysteinemia
OT  - Microglia
OT  - Neuroinflammation
COIS- The authors declare that they have no competing interests.
EDAT- 2020/09/19 06:00
MHDA- 2021/07/22 06:00
PMCR- 2020/09/17
CRDT- 2020/09/18 05:33
PHST- 2020/02/13 00:00 [received]
PHST- 2020/08/24 00:00 [accepted]
PHST- 2020/09/18 05:33 [entrez]
PHST- 2020/09/19 06:00 [pubmed]
PHST- 2021/07/22 06:00 [medline]
PHST- 2020/09/17 00:00 [pmc-release]
AID - 10.1186/s12974-020-01938-7 [pii]
AID - 1938 [pii]
AID - 10.1186/s12974-020-01938-7 [doi]
PST - epublish
SO  - J Neuroinflammation. 2020 Sep 17;17(1):274. doi: 10.1186/s12974-020-01938-7.