PMID- 33410588
OWN - NLM
STAT- MEDLINE
DCOM- 20211118
LR  - 20211118
IS  - 1552-5279 (Electronic)
IS  - 1552-5260 (Linking)
VI  - 17
IP  - 7
DP  - 2021 Jul
TI  - Increased beta-site APP cleaving enzyme 1-mediated insulin receptor cleavage in type 
      2 diabetes mellitus with cognitive impairment.
PG  - 1097-1108
LID - 10.1002/alz.12276 [doi]
AB  - INTRODUCTION: Patients with type 2 diabetes mellitus (T2DM) are at a high risk of 
      cognitive impairment, with insulin resistance playing a pivotal role. beta-site 
      amyloid precursor protein cleaving enzyme 1 (BACE1) is considered a predictor of 
      Alzheimer's disease. However, the potential roles of BACE1 in insulin resistance 
      and the risk of cognitive impairment in T2DM remain unclear. METHODS: We measured 
      plasma BACE1 levels, BACE1 cleavage activities for Swedish mutant amyloid 
      precursor protein (APPsw) and insulin receptor beta subunit (INSR-beta), and soluble 
      INSR (sINSR) levels in a clinical cohort study. RESULTS: T2DM patients with or 
      without cognitive impairment exhibited elevated plasma BACE1 levels and BACE1 
      enzymatic activities for APPsw and INSR-beta, and sINSR levels. Moreover, the 
      glycemic status correlated with elevated BACE1 levels and BACE1-mediated INSR 
      cleavage, which was associated with insulin resistance. DISCUSSION: The elevated 
      BACE1 levels in T2DM may contribute to increasing the cognitive impairment risk 
      through both amyloidogenesis and insulin resistance.
CI  - (c) 2021 the Alzheimer's Association.
FAU - Bao, Hong
AU  - Bao H
AD  - Neurodegenerative Disorder Research Center, Division of Life Sciences and 
      Medicine, University of Science and Technology of China, Hefei, China.
FAU - Liu, Yiming
AU  - Liu Y
AD  - Neurodegenerative Disorder Research Center, Division of Life Sciences and 
      Medicine, University of Science and Technology of China, Hefei, China.
FAU - Zhang, Mengguo
AU  - Zhang M
AD  - Neurodegenerative Disorder Research Center, Division of Life Sciences and 
      Medicine, University of Science and Technology of China, Hefei, China.
FAU - Chen, Zuolong
AU  - Chen Z
AD  - Neurodegenerative Disorder Research Center, Division of Life Sciences and 
      Medicine, University of Science and Technology of China, Hefei, China.
FAU - Zhang, Weiwei
AU  - Zhang W
AD  - Institute on Aging and Brain Disorders, First Affiliated Hospital of University 
      of Science and Technology of China, Hefei, China.
FAU - Ge, Yuhao
AU  - Ge Y
AD  - Institute on Aging and Brain Disorders, First Affiliated Hospital of University 
      of Science and Technology of China, Hefei, China.
FAU - Kang, Dongmei
AU  - Kang D
AD  - Institute on Aging and Brain Disorders, First Affiliated Hospital of University 
      of Science and Technology of China, Hefei, China.
FAU - Gao, Feng
AU  - Gao F
AD  - Neurodegenerative Disorder Research Center, Division of Life Sciences and 
      Medicine, University of Science and Technology of China, Hefei, China.
AD  - Institute on Aging and Brain Disorders, First Affiliated Hospital of University 
      of Science and Technology of China, Hefei, China.
FAU - Shen, Yong
AU  - Shen Y
AD  - Neurodegenerative Disorder Research Center, Division of Life Sciences and 
      Medicine, University of Science and Technology of China, Hefei, China.
AD  - Institute on Aging and Brain Disorders, First Affiliated Hospital of University 
      of Science and Technology of China, Hefei, China.
AD  - Center for Excellence in Brain Science and Intelligence Technology, Chinese 
      Academy of Sciences, Shanghai, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210107
PL  - United States
TA  - Alzheimers Dement
JT  - Alzheimer's & dementia : the journal of the Alzheimer's Association
JID - 101231978
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - EC 2.7.10.1 (Receptor, Insulin)
RN  - EC 3.4.- (Amyloid Precursor Protein Secretases)
RN  - EC 3.4.23.- (Aspartic Acid Endopeptidases)
RN  - EC 3.4.23.46 (BACE1 protein, human)
SB  - IM
MH  - Aged
MH  - Alzheimer Disease/metabolism
MH  - Amyloid Precursor Protein Secretases/*blood
MH  - Amyloid beta-Protein Precursor/metabolism
MH  - Aspartic Acid Endopeptidases
MH  - Cognitive Dysfunction/*diagnosis
MH  - Cohort Studies
MH  - Diabetes Mellitus, Type 2/blood/*complications
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Receptor, Insulin/*blood
OTO - NOTNLM
OT  - T2DM with cognitive impairment
OT  - cognitive impairment
OT  - plasma BACE1 enzymatic activity for APPsw
OT  - plasma BACE1 enzymatic activity for INSR-beta
OT  - plasma BACE1 levels
OT  - sINSR levels
OT  - type 2 diabetes mellitus
EDAT- 2021/01/08 06:00
MHDA- 2021/11/19 06:00
CRDT- 2021/01/07 08:41
PHST- 2020/11/17 00:00 [revised]
PHST- 2020/08/26 00:00 [received]
PHST- 2020/11/19 00:00 [accepted]
PHST- 2021/01/08 06:00 [pubmed]
PHST- 2021/11/19 06:00 [medline]
PHST- 2021/01/07 08:41 [entrez]
AID - 10.1002/alz.12276 [doi]
PST - ppublish
SO  - Alzheimers Dement. 2021 Jul;17(7):1097-1108. doi: 10.1002/alz.12276. Epub 2021 
      Jan 7.