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By Hooper N.M. (ed.)

This article brings jointly the most thoughts of biochemistry, mobilephone biology, and molecular biology which are getting used to enquire the molecular foundation of Alzheimer's affliction. It offers a precis of presently to be had healing brokers and customers for destiny medicines.

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Example text

The K variant of the butyrylcholinesterase (BCHE) gene was reported by Lehmann and colleagues (106) to be associated with AD in carriers of the Apo ε4 allele. The excess of K-variant carriers in LOAD was replicated by Sandbrink et al. (107), but they found no major interaction between BCHE-K and ApoE. At least two other studies (108,109) have been unable to confirm this association of BCHE-K with sporadic disease, and analysis of the segregation of microsatellite markers flanking the gene on chromosome 3 in AD kindreds suggested that there is no gene in linkage disequilibrium with BCHE-K contributing to familial disease (108).

J. Biol. Chem. 273, 16,470–16,475. 80. Schellenberg, G. , Deeb, S. , Bryant, E. , Martin, G. , Lampe, T. , and Bird, T. D. (1987) Association of apolipoprotein CII with familial dementia of the Alzheimer type. J. Neurogenet. 4, 97–108. 81. Schellenberg, G. , Wijsman, E. , Moore, D. , Martin, G. , and Bird, T. D. (1992) Genetic association and linkage analysis of the Ap°CII locus and familial Alzheimer’s disease. Ann. Neurol. 31, 223–227. 82. Bullido, M. , Artiga, M. , Garcia, M. , et al. (1998).

1. Cholinesterase Inhibitors As of this writing (May 1998), there are said to be over a dozen CEIs in various stages of clinical development, but only six of them have clinical trial data that has been presented in public. This chapter summarizes the findings with tacrine (TAC) (25), donepezil (DON) (26a), rivastigmine (RIV) (27a), and metrifonate (MET) (23). 1. General Comments All of these agents have a narrow therapeutic window. Efficacy is strongly dose dependent, however. Peripheral tolerance to the gastrointestinal side effects develops slowly; hence, all of the agents must be titrated slowly.

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