Hyperhomocysteinemic Alzheimer's mouse model of amyloidosis shows increased brain amyloid beta peptide levels

Neurobiology of Disease
Javier Pacheco-QuintoM A Pappolla

Abstract

Recent epidemiological and clinical data suggest that elevated serum homocysteine levels may increase the risk of developing Alzheimer's disease (AD), but the underlying mechanisms are unknown. We tested the hypothesis that high serum homocysteine concentration may increase amyloid beta-peptide (Abeta) levels in the brain and could therefore accelerate AD neuropathology. For this purpose, we mated a hyperhomocysteinemic CBS(tm1Unc) mouse carrying a heterozygous dominant mutation in cystathionine-beta-synthase (CBS*) with the APP*/PS1* mouse model of brain amyloidosis. The APP*/PS1*/CBS* mice showed significant elevations of serum homocysteine levels compared to the double transgenic APP*/PS1* model of amyloidosis. Results showed that female (but not male) APP*/PS1*/CBS* mice exhibited significant elevations of Abeta40 and Abeta42 levels in the brain. Correlations between homocysteine levels in serum and brain Abeta levels were statistically significant. No increases in beta secretase activity or evidence of neuronal cell loss in the hyperhomocysteinemic mice were found. The causes of neuronal dysfunction and degeneration in AD are not fully understood, but increased production of Abeta seems to be of major importance. By unveil...Continue Reading

References

Feb 28, 1995·Proceedings of the National Academy of Sciences of the United States of America·M WatanabeN Maeda
May 27, 1997·Proceedings of the National Academy of Sciences of the United States of America·S A LiptonJ S Stamler
May 16, 2000·Arteriosclerosis, Thrombosis, and Vascular Biology·D W Jacobsen
Jul 20, 2001·Journal of Neurochemistry·P I HoT B Shea
Feb 15, 2002·The New England Journal of Medicine·Sudha SeshadriPhilip A Wolf
Jan 13, 2005·American Journal of Physiology. Endocrinology and Metabolism·Connie W H WooKarmin O

❮ Previous
Next ❯

Citations

Oct 5, 2010·The Journal of Biological Chemistry·Hirohisa MinagawaMakoto Michikawa
May 28, 2010·Neuropsychiatric Disease and Treatment·Steven F Werder
Feb 24, 2010·The Biochemical Journal·Kirsty E A MuirheadFrank J Gunn-Moore
Mar 22, 2014·Frontiers in Molecular Neuroscience·Jean-Marie Sontag, Estelle Sontag
Jul 20, 2016·Annual Review of Nutrition·A David Smith, Helga Refsum
Oct 25, 2016·International Journal of Molecular Sciences·Henrieta ŠkovierováJán Lehotský
Nov 24, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Xiao-Ang LiW L Wendy Hsiao
Apr 7, 2017·Scientific Reports·Jian-Guo LiDomenico Praticò
Jul 6, 2007·Expert Review of Neurotherapeutics·Remi DosunmuNasser H Zawia
Feb 25, 2014·American Journal of Alzheimer's Disease and Other Dementias·Jin QiaoQiu-Min Qu
Dec 20, 2017·Journal of Alzheimer's Disease : JAD·Antonio Di MecoDomenico Praticò
Nov 30, 2018·Chemical Record : an Official Publication of the Chemical Society of Japan ... [et Al.]·Manuela Bartolini, José Marco-Contelles
Jul 16, 2019·The Journal of Pharmacy and Pharmacology·Seetha HarilalBijo Mathew
Apr 24, 2020·Current Pharmaceutical Design·Anmol DograJasjeet K Narang
Dec 28, 2006·Neurochemical Research·José A LuchsingerRichard Mayeux
Jun 5, 2018·Neural Regeneration Research·Hong-Bin LuoJun-Xu Li
Nov 20, 2012·Journal of Neurochemistry·Gao-Shang ChaiGong-Ping Liu
Feb 7, 2020·Pharmaceuticals·Carla Montecinos-OlivaNibaldo C Inestrosa
May 19, 2020·Current Pharmaceutical Design·Zeba MueedNitesh K Poddar
May 18, 2021·Frontiers in Bioengineering and Biotechnology·Nazeer Hussain KhanXin-Ying Ji
Jun 15, 2021·Frontiers in Aging Neuroscience·Qianwen WangRuixia Zhu
Jul 3, 2021·International Journal of Molecular Sciences·Amany TawfikPragya Rajpurohit
Jun 21, 2011·Trends in Pharmacological Sciences·Jia-Min ZhuoDomenico Praticò

❮ Previous
Next ❯

Related Concepts

Related Feeds

ApoE, Lipids & Cholesterol

Serum cholesterol, triglycerides, apolipoprotein B (APOB)-containing lipoproteins (very low-density lipoprotein (VLDL), immediate-density lipoprotein (IDL), and low-density lipoprotein (LDL), lipoprotein A (LPA)) and the total cholesterol/high-density lipoprotein (HDL) cholesterol ratio are all connected in diseases. Here is the latest research.

Alzheimer's Disease: APP

Amyloid precursor protein (APP) proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques in the brain. Here is the latest research on APP and Alzheimer's disease.

Alzheimer's Disease: Animal Models

Alzheimer's disease is a neurodegenerative disease which can be studied using various experimental systems. This feed focuses on animal models used for Alzheimer's disease research.

Alzheimer's Disease: APOE

Apolipoprotein E (APOE) polymorphic alleles are major genetic risk factors for Alzheimer's disease. Discover the latest research on APOE and other genetic determinants of Alzheimer's disease here.

Alzheimer's Disease: Amyloid Beta

Alzheimer's disease is a neurodegenerative disease associated with the accumulation of amyloid plaques in the brain; these plaques are comprised of amyloid beta deposits. Here is the latest research in this field.

Epidemiology of Aging

This feed focuses on epidemiology of aging and aging-related conditions, including Alzheimer’s disease, dementia, and age-associated cognitive impairment. Here is the latest research.

Astrocytes & Amyloid

Astrocytes are thought to play a role in amyloid production and have been implicated in neurodegenerative diseases such as Alzheimer’s disease. Here is the latest research on the relationship between astrocytes and amyloid.

ApoE Phenotypes

Apolipoprotein E (APOE) is a protein involved in fat metabolism and associated with the pathogenesis of Alzheimer's disease and cardiovascular disease. Here is the latest research on APOE phenotypes.