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Limited Alzheimer-type neurodegeneration in experimental obesity and type 2 diabetes mellitus.
J Alzheimers Dis 2008; 15(1):29-44JA

Abstract

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.

Authors+Show Affiliations

Department of Medicine, Rhode Island Hospital and the Warren Alpert Medical School of Brown University, Providence, RI 02903, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18780965

Citation

Moroz, Natalie, et al. "Limited Alzheimer-type Neurodegeneration in Experimental Obesity and Type 2 Diabetes Mellitus." Journal of Alzheimer's Disease : JAD, vol. 15, no. 1, 2008, pp. 29-44.
Moroz N, Tong M, Longato L, et al. Limited Alzheimer-type neurodegeneration in experimental obesity and type 2 diabetes mellitus. J Alzheimers Dis. 2008;15(1):29-44.
Moroz, N., Tong, M., Longato, L., Xu, H., & de la Monte, S. M. (2008). Limited Alzheimer-type neurodegeneration in experimental obesity and type 2 diabetes mellitus. Journal of Alzheimer's Disease : JAD, 15(1), pp. 29-44.
Moroz N, et al. Limited Alzheimer-type Neurodegeneration in Experimental Obesity and Type 2 Diabetes Mellitus. J Alzheimers Dis. 2008;15(1):29-44. PubMed PMID: 18780965.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Limited Alzheimer-type neurodegeneration in experimental obesity and type 2 diabetes mellitus. AU - Moroz,Natalie, AU - Tong,Ming, AU - Longato,Lisa, AU - Xu,Haiyan, AU - de la Monte,Suzanne M, PY - 2008/9/11/pubmed PY - 2008/11/19/medline PY - 2008/9/11/entrez SP - 29 EP - 44 JF - Journal of Alzheimer's disease : JAD JO - J. Alzheimers Dis. VL - 15 IS - 1 N2 - 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. SN - 1387-2877 UR - https://www.unboundmedicine.com/medline/citation/18780965/Limited_Alzheimer_type_neurodegeneration_in_experimental_obesity_and_type_2_diabetes_mellitus_ L2 - https://content.iospress.com/openurl?genre=article&issn=1387-2877&volume=15&issue=1&spage=29 DB - PRIME DP - Unbound Medicine ER -