PMID- 18780965
OWN - NLM
STAT- MEDLINE
DCOM- 20081118
LR  - 20230407
IS  - 1387-2877 (Print)
IS  - 1875-8908 (Electronic)
IS  - 1387-2877 (Linking)
VI  - 15
IP  - 1
DP  - 2008 Sep
TI  - Limited Alzheimer-type neurodegeneration in experimental obesity and type 2 
      diabetes mellitus.
PG  - 29-44
AB  - Alzheimer's disease (AD) is associated with brain insulin resistance and insulin 
      deficiency, whereas Type 2 diabetes mellitus (T2DM) is associated with peripheral 
      insulin resistance. This study assesses the degree to which T2DM causes AD-type 
      neurodegeneration. In a C57BL/6 mouse model of obesity and T2DM, we characterized 
      the histopathology, gene expression, and insulin and insulin-like growth factor 
      (IGF)-receptor binding in temporal lobe. High fat diet (HFD) feeding for 16 weeks 
      doubled mean body weight, caused T2DM, and marginally reduced mean brain weight. 
      These effects were associated with significantly increased levels of tau, IGF-I 
      receptor, insulin receptor substrate-1 (IRS-1), IRS-4, ubiquitin, glial 
      fibrillary acidic protein, and 4-hydroxynonenol, and decreased expression of 
      beta-actin. HFD feeding also caused brain insulin resistance manifested by 
      reduced BMAX for insulin receptor binding, and modestly increased brain insulin 
      gene expression. However, HFD-fed mouse brains did not exhibit AD histopathology, 
      increases in amyloid-beta or phospho-tau, or impairments in IGF signaling or 
      acetylcholine homeostasis. Obesity and T2DM cause brain atrophy with insulin 
      resistance, oxidative stress, and cytoskeleton degradation, but the absence of 
      many features that typify AD suggests that obesity and T2DM may contribute to, 
      but are not sufficient to cause AD.
FAU - Moroz, Natalie
AU  - Moroz N
AD  - Department of Medicine, Rhode Island Hospital and the Warren Alpert Medical 
      School of Brown University, Providence, RI 02903, USA.
FAU - Tong, Ming
AU  - Tong M
FAU - Longato, Lisa
AU  - Longato L
FAU - Xu, Haiyan
AU  - Xu H
FAU - de la Monte, Suzanne M
AU  - de la Monte SM
LA  - eng
GR  - AA02666/AA/NIAAA NIH HHS/United States
GR  - R37 AA011431/AA/NIAAA NIH HHS/United States
GR  - AA12908/AA/NIAAA NIH HHS/United States
GR  - AA16126/AA/NIAAA NIH HHS/United States
GR  - R01 AA012908/AA/NIAAA NIH HHS/United States
GR  - R56 AA011431/AA/NIAAA NIH HHS/United States
GR  - AA11431/AA/NIAAA NIH HHS/United States
GR  - AA02169/AA/NIAAA NIH HHS/United States
GR  - R01 AA011431/AA/NIAAA NIH HHS/United States
GR  - R37 AA002666/AA/NIAAA NIH HHS/United States
GR  - K24 AA016126/AA/NIAAA NIH HHS/United States
GR  - R01 AA002666/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - J Alzheimers Dis
JT  - Journal of Alzheimer's disease : JAD
JID - 9814863
RN  - 0 (Actins)
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Aldehydes)
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (DNA Primers)
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (Insulin Receptor Substrate Proteins)
RN  - 0 (Irs1 protein, mouse)
RN  - 0 (RNA, Messenger)
RN  - 0 (Ubiquitin)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - K1CVM13F96 (4-hydroxy-2-nonenal)
SB  - IM
MH  - Actins/metabolism
MH  - Adaptor Proteins, Signal Transducing/metabolism
MH  - Aldehydes/metabolism
MH  - Alzheimer Disease/genetics/metabolism/*pathology
MH  - Amyloid beta-Peptides/metabolism
MH  - Animals
MH  - Atrophy/metabolism/pathology
MH  - Brain/metabolism/*pathology
MH  - DNA Primers/genetics
MH  - Diabetes Mellitus, Type 2/*metabolism
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Gene Expression/genetics
MH  - Glial Fibrillary Acidic Protein/metabolism
MH  - Insulin Receptor Substrate Proteins
MH  - Insulin Resistance/physiology
MH  - Insulin-Like Growth Factor I/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Nerve Degeneration/genetics/metabolism/*pathology
MH  - Obesity/*metabolism
MH  - RNA, Messenger/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Ubiquitin/metabolism
PMC - PMC10074393
MID - NIHMS1875992
EDAT- 2008/09/11 09:00
MHDA- 2008/11/19 09:00
PMCR- 2023/04/05
CRDT- 2008/09/11 09:00
PHST- 2008/09/11 09:00 [pubmed]
PHST- 2008/11/19 09:00 [medline]
PHST- 2008/09/11 09:00 [entrez]
PHST- 2023/04/05 00:00 [pmc-release]
AID - 10.3233/jad-2008-15103 [doi]
PST - ppublish
SO  - J Alzheimers Dis. 2008 Sep;15(1):29-44. doi: 10.3233/jad-2008-15103.