PMID- 28467789
OWN - NLM
STAT- MEDLINE
DCOM- 20180329
LR  - 20181113
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 8
IP  - 27
DP  - 2017 Jul 4
TI  - Chronic diabetic states worsen Alzheimer neuropathology and cognitive deficits 
      accompanying disruption of calcium signaling in leptin-deficient APP/PS1 mice.
PG  - 43617-43634
LID - 10.18632/oncotarget.17116 [doi]
AB  - The coincidences between Alzheimer's disease (AD) and type 2 diabetes mellitus 
      (T2DM) are so compelling that it is attractive to speculate that diabetic 
      conditions might aggravate AD pathologies by calcium dysfunction, although the 
      understanding of the molecular mechanisms involved remains elusive. The present 
      work was undertaken to investigate whether calcium dyshomeostasis is associated 
      with the exacerbated Alzheimer-like cognitive dysfunction observed in diabetic 
      conditions in APP/PS1-ob/ob mice, which were generated by crossing ob/ob mice 
      with APP/PS1 mice. We confirmed that the diabetic condition can aggravate not 
      only Abeta deposition but also tau phosphorylation, synaptic loss, neuronal death, 
      and inflammation, exacerbating cognitive impairment in AD mice. More importantly, 
      we found that the diabetic condition dramatically elevated calcium levels in 
      APP/PS1 mice, thereby stimulating the phosphorylation of the calcium-dependent 
      kinases. Our findings suggest that controlling over-elevation of intracellular 
      calcium may provide novel insights for approaching AD in diabetic patients and 
      delaying AD progression.
FAU - Zhang, Shuai
AU  - Zhang S
AD  - College of Life and Health Sciences, Northeastern University, Shenyang, China.
FAU - Chai, Rui
AU  - Chai R
AD  - College of Life and Health Sciences, Northeastern University, Shenyang, China.
FAU - Yang, Ying-Ying
AU  - Yang YY
AD  - College of Life and Health Sciences, Northeastern University, Shenyang, China.
FAU - Guo, Shi-Qi
AU  - Guo SQ
AD  - College of Life and Health Sciences, Northeastern University, Shenyang, China.
FAU - Wang, Shan
AU  - Wang S
AD  - College of Life and Health Sciences, Northeastern University, Shenyang, China.
FAU - Guo, Tian
AU  - Guo T
AD  - College of Life and Health Sciences, Northeastern University, Shenyang, China.
FAU - Xu, Shuang-Feng
AU  - Xu SF
AD  - College of Life and Health Sciences, Northeastern University, Shenyang, China.
FAU - Zhang, Yan-Hui
AU  - Zhang YH
AD  - College of Life and Health Sciences, Northeastern University, Shenyang, China.
FAU - Wang, Zhan-You
AU  - Wang ZY
AD  - College of Life and Health Sciences, Northeastern University, Shenyang, China.
FAU - Guo, Chuang
AU  - Guo C
AD  - College of Life and Health Sciences, Northeastern University, Shenyang, China.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Leptin)
RN  - 0 (tau Proteins)
SB  - IM
MH  - Alzheimer Disease/*etiology/*metabolism/psychology
MH  - Amyloid beta-Peptides/metabolism
MH  - Animals
MH  - Brain/metabolism/pathology/physiopathology
MH  - *Calcium Signaling
MH  - *Cognitive Dysfunction
MH  - Diabetes Mellitus, Type 2/*complications
MH  - Disease Models, Animal
MH  - Humans
MH  - Inflammation
MH  - Leptin/*deficiency
MH  - Male
MH  - Memory Disorders/genetics
MH  - Mice
MH  - Mice, Transgenic
MH  - Phosphorylation
MH  - Protein Aggregation, Pathological/genetics
MH  - Signal Transduction
MH  - Synapses/genetics/metabolism
MH  - tau Proteins/metabolism
PMC - PMC5546429
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - calcium
OT  - diabetes mellitus
OT  - tau
OT  - beta-amyloid
COIS- CONFLICTS OF INTEREST The authors declare that no competing interests exist.
EDAT- 2017/05/04 06:00
MHDA- 2018/03/30 06:00
PMCR- 2017/07/04
CRDT- 2017/05/04 06:00
PHST- 2017/02/27 00:00 [received]
PHST- 2017/04/03 00:00 [accepted]
PHST- 2017/05/04 06:00 [pubmed]
PHST- 2018/03/30 06:00 [medline]
PHST- 2017/05/04 06:00 [entrez]
PHST- 2017/07/04 00:00 [pmc-release]
AID - 17116 [pii]
AID - 10.18632/oncotarget.17116 [doi]
PST - ppublish
SO  - Oncotarget. 2017 Jul 4;8(27):43617-43634. doi: 10.18632/oncotarget.17116.