Diabetes Mellitus Induces Alzheimer's Disease Pathology: Histopathological Evidence from Animal Models

被引:93
作者
Kimura, Nobuyuki [1 ]
机构
[1] Natl Ctr Geriatr & Gerontol, Ctr Dev Adv Med Dementia, Dept Alzheimers Dis Res, Sect Cell Biol & Pathol, Gengo 35, Aichi 4748511, Japan
关键词
Alzheimer's disease; animal model; diabetes mellitus; insulin resistance; pathology; AMYLOID-BETA-PROTEIN; TRANSGENIC MOUSE MODEL; GLYCOGEN-SYNTHASE KINASE-3; MILD COGNITIVE IMPAIRMENT; A-BETA; INSULIN-RESISTANCE; TAU-PROTEIN; PRECURSOR PROTEIN; IN-VIVO; INTRACEREBROVENTRICULAR INJECTION;
D O I
10.3390/ijms17040503
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Alzheimer's disease (AD) is the major causative disease of dementia and is characterized pathologically by the accumulation of senile plaques (SPs) and neurofibrillary tangles (NFTs) in the brain. Although genetic studies show that beta-amyloid protein (A beta), the major component of SPs, is the key factor underlying AD pathogenesis, it remains unclear why advanced age often leads to AD. Interestingly, several epidemiological and clinical studies show that type II diabetes mellitus (DM) patients are more likely to exhibit increased susceptibility to AD. Moreover, growing evidence suggests that there are several connections between the neuropathology that underlies AD and DM, and there is evidence that the experimental induction of DM can cause cognitive dysfunction, even in rodent animal models. This mini-review summarizes histopathological evidence that DM induces AD pathology in animal models and discusses the possibility that aberrant insulin signaling is a key factor in the induction of AD pathology.
引用
收藏
页数:11
相关论文
共 130 条
[41]   Amyloid, the presenilins and Alzheimer's disease [J].
Hardy, J .
TRENDS IN NEUROSCIENCES, 1997, 20 (04) :154-159
[42]   Medicine - The amyloid hypothesis of Alzheimer's disease: Progress and problems on the road to therapeutics [J].
Hardy, J ;
Selkoe, DJ .
SCIENCE, 2002, 297 (5580) :353-356
[43]   Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease [J].
Harold, Denise ;
Abraham, Richard ;
Hollingworth, Paul ;
Sims, Rebecca ;
Gerrish, Amy ;
Hamshere, Marian L. ;
Pahwa, Jaspreet Singh ;
Moskvina, Valentina ;
Dowzell, Kimberley ;
Williams, Amy ;
Jones, Nicola ;
Thomas, Charlene ;
Stretton, Alexandra ;
Morgan, Angharad R. ;
Lovestone, Simon ;
Powell, John ;
Proitsi, Petroula ;
Lupton, Michelle K. ;
Brayne, Carol ;
Rubinsztein, David C. ;
Gill, Michael ;
Lawlor, Brian ;
Lynch, Aoibhinn ;
Morgan, Kevin ;
Brown, Kristelle S. ;
Passmore, Peter A. ;
Craig, David ;
McGuinness, Bernadette ;
Todd, Stephen ;
Holmes, Clive ;
Mann, David ;
Smith, A. David ;
Love, Seth ;
Kehoe, Patrick G. ;
Hardy, John ;
Mead, Simon ;
Fox, Nick ;
Rossor, Martin ;
Collinge, John ;
Maier, Wolfgang ;
Jessen, Frank ;
Schuermann, Britta ;
van den Bussche, Hendrik ;
Heuser, Isabella ;
Kornhuber, Johannes ;
Wiltfang, Jens ;
Dichgans, Martin ;
Froelich, Lutz ;
Hampel, Harald ;
Huell, Michael .
NATURE GENETICS, 2009, 41 (10) :1088-U61
[44]   Diet-induced insulin resistance promotes amyloidosis in a transgenic mouse model of Alzheimer's disease [J].
Ho, L ;
Qin, WP ;
Pompl, PN ;
Xiang, ZM ;
Wang, J ;
Zhao, Z ;
Peng, YZ ;
Cambareri, G ;
Rocher, A ;
Mobbs, CV ;
Hof, PR ;
Pasinetti, GM .
FASEB JOURNAL, 2004, 18 (03) :902-+
[45]  
Hoyer S, 1994, J Neural Transm Suppl, V44, P259
[46]   Insulin enhances mitochondrial inner membrane potential and increases ATP levels through phosphoinositide 3-kinase in adult sensory neurons [J].
Huang, TJ ;
Verkhratsky, A ;
Fernyhough, P .
MOLECULAR AND CELLULAR NEUROSCIENCE, 2005, 28 (01) :42-54
[47]  
Imahori K, 1997, J BIOCHEM, V121, P179
[48]   Tau pathology in Alzheimer disease and other tauopathies [J].
Iqbal, K ;
Alonso, ADC ;
Chen, S ;
Chohan, MO ;
El-Akkad, E ;
Gong, CX ;
Khatoon, S ;
Li, B ;
Liu, F ;
Rahman, A ;
Tanimukai, H ;
Grundke-Iqbal, I .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 2005, 1739 (2-3) :198-210
[49]   PHOSPHORYLATION SITES ON TAU BY TAU PROTEIN KINASE-I, A BOVINE DERIVED KINASE GENERATING AN EPITOPE OF PAIRED HELICAL FILAMENTS [J].
ISHIGURO, K ;
OMORI, A ;
TAKAMATSU, M ;
SATO, K ;
ARIOKA, M ;
UCHIDA, T ;
IMAHORI, K .
NEUROSCIENCE LETTERS, 1992, 148 (1-2) :202-206
[50]   Identification of the major Aβ1-42-degrading catabolic pathway in brain parenchyma:: Suppression leads to biochemical and pathological deposition [J].
Iwata, N ;
Tsubuki, S ;
Takaki, Y ;
Watanabe, K ;
Sekiguchi, M ;
Hosoki, E ;
Kawashima-Morishima, M ;
Lee, HJ ;
Hama, E ;
Sekine-Aizawa, Y ;
Saido, TC .
NATURE MEDICINE, 2000, 6 (02) :143-150