The apolipoprotein E ε4 allele and the response to tacrine therapy in Alzheimer’s disease

The objective of our study was to evaluate the effects of the apolipoprotein E (ApoE) phenotype and gender on the response to tacrine treatment in Alzheimer’s disease (AD). ApoE phenotyping was performed on 76 patients treated with tacrine for AD. This group comprised 33 ApoE ε4 allele carriers (ε4+) and 43 non‐ε4 carriers (ε4–). Patients were treated blindly in relation to the ApoE phenotype, with incremental tacrine dosages ranging from 40 mg/day up to the highest dosage (160 mg) tolerated without side‐effects. At least 6 weeks elapsed between each increase. Changes in the scores for the Alzheimer Disease Assessment Scale‐Cognitive Component (ADAS‐Cog) between baseline and each increment in dosage were assessed in the ε4– and ε4+ groups. The cut‐off point for being considered as responsive to tacrine treatment was a 4‐point decrease in the ADAS‐Cog score.

[1]  P. Amouyel,et al.  Apolipoprotein E phenotypes in demented and cognitively impaired patients with and without cerebrovascular disease , 1999, European journal of neurology.

[2]  Antoinette Jobert,et al.  In vivo PET study of cerebral [11C] methyltetrahydroaminoacridine distribution and kinetics in healthy human subjects , 1999, European journal of neurology.

[3]  H. Soininen,et al.  Tetrahydroaminoacridine improves the recency effect in Alzheimer's disease , 1998, Neuroscience.

[4]  G. Wilcock,et al.  Effect of gender and apolipoprotein E genotype on response to anticholinesterase therapy in Alzheimer's disease , 1998, International journal of geriatric psychiatry.

[5]  J. Poirier,et al.  Treatment outcome of tacrine therapy depends on apolipoprotein genotype and gender of the subjects with Alzheimer's disease , 1998, Neurology.

[6]  M. Memo,et al.  Lewy-body dementia and responsiveness to cholinesterase inhibitors: a paradigm for heterogeneity of Alzheimer's disease? , 1996, Trends in pharmacological sciences.

[7]  D. Raichvarg,et al.  Direct phenotyping of human apolipoprotein E in plasma: application to population frequency distribution in Paris (France). , 1993, Human heredity.

[8]  S. E. Freeman,et al.  Tacrine: A pharmacological review , 1991, Progress in Neurobiology.

[9]  M. Pericak-Vance,et al.  Apolipoprotein E and Alzheimer’s Disease: State of the Field After Two Years , 1996 .

[10]  T. Junthé,et al.  Pharmacokinetics of tetrahydroaminoacridine: relations to clinical and biochemical effects in Alzheimer patients , 1992, International clinical psychopharmacology.

[11]  K. Davis,et al.  The Alzheimer's disease assessment scale: an instrument for assessing treatment efficacy. , 1983, Psychopharmacology bulletin.