Text Box: Tau Text Box: App       

                                            

                                                

                                                                                      

Text Box: Apoe     

Alzheimerˇ¦s

Parkinsonism

 

 


                                         

               

Text Box: beta2-ArText Box: nAChRs                                                     

 

                                      

                     

   2009/7/2              

J Neurochem. 2008 Sep;106(6):2263-71. Epub 2008 Jun 28.Click here to read Links

Functional interactions of APP with the apoE receptor family.

Hoe HS, Rebeck GW.

Department of Neuroscience, Georgetown University, Washington, District of Columbia 20007, USA.

The beta-amyloid precursor protein (APP) is central to the pathogenesis of Alzheimer's disease, but its normal functions in the brain are poorly understood. A number of APP-interacting proteins have been identified: intracellularly, APP interacts with adaptor proteins through its conserved NPXY domain; extracellularly, APP interacts with a component of the extracellular matrix, F-spondin. Interestingly, many of these APP-interacting proteins also interact with the family of receptors for apolipoprotein E (apoE), the Alzheimer's disease risk factor. apoE receptors also share with APP the fact that they are cleaved by the same secretase activities. apoE receptors are shed from the cell surface, a cleavage that is regulated by receptor-ligand interactions, and C-terminal fragments of apoE receptors are cleaved by gamma-secretase. Functionally, both APP and apoE receptors affect neuronal migration and synapse formation in the brain. This review summarizes these numerous interactions between APP and apoE receptors, which provide clues about the normal functions of APP.

PMID: 18554321 [PubMed - indexed for MEDLINE

Brain Res. 2008 May 19;1210:216-22. Epub 2008 Mar 20.Click here to read Links

Polymorphisms at the beta2-adrenergic receptor gene influence Alzheimer's disease susceptibility.

Yu JT, Tan L, Ou JR, Zhu JX, Liu K, Song JH, Sun YP.

Department of Neurology, Qingdao Municipal Hospital, Affiliated Hospital of Qingdao University Medical College, Shandong Province, PR China.

Increasing evidence indicates that the beta2-adrenergic receptor (beta2-AR) may play an important role in Alzheimer's disease (AD). We investigated the effect of two polymorphisms in the beta2-AR gene: Gly16Arg and Gln27Glu for the risk of sporadic Late Onset Alzheimer's Disease (LOAD) in 109 patients and 109 healthy controls matched for sex and age in a Han Chinese population. Results revealed that both the 16Gly allele and the 27Glu allele of the beta2-AR gene were associated with an increased risk of LOAD (P=0.009, OR=1.652 and P=0.002, OR=2.846, respectively), and they also showed a highly significant interaction with the Apolipoprotein E gene (APOE) epsilon4 allele (OR=4.200 and 9.441, respectively). Examination of the haplotypes identified the Gly16Glu27 haplotype to increase the risk of LOAD (P=0.004). Our results suggest that variations in the beta2-AR gene play an important role in the pathogenesis of sporadic LOAD, and interact with the epsilon4 allele to markedly increase the LOAD risk.

Brain Res Bull. 2009 Apr 29;79(2):111-5. Epub 2009 Jan 29.Click here to read Links

Hippocampal infusions of apolipoprotein E peptides induce long-lasting cognitive impairment.

Eddins D, Klein RC, Yakel JL, Levin ED.

Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, United States.

The inheritance of the varepsilon4 allele of apolipoprotein E (ApoE4) and cholinergic system dysfunction have long been associated with the pathology of Alzheimer's disease (AD). Recently, in vitro studies have established a direct link between ApoE and cholinergic function in that synthetic peptides containing segments of the ApoE protein (ApoE(133-149) and ApoE(141-148)) interact with alpha7 nicotinic acetylcholine receptors (nAChRs) in the hippocampus. This raises the possibility that ApoE peptides may contribute to cognitive impairment in AD in that the hippocampus plays a key role in cognitive functioning. To test this, we acutely infused ApoE peptides into the ventral hippocampus of female Sprague-Dawley rats and assessed the resultant effects on radial-arm maze choice accuracy over a period of weeks after the infusion. Local ventral hippocampal infusion of ApoE peptides caused significant cognitive impairment in radial-arm maze learning that persisted several weeks after the acute infusion. This persisting deficit may be an important model for understanding the relationship between ApoE protein-induced neurotoxicity and cognitive impairment as well as serve as a platform for the development of new therapies to avoid neurotoxicity and cognitive decline.