摘要
Background: It has been proposed that, independent of the 4 allele, APOE prom oter polymorphisms (- 491 A/T and 219 G/T) may be risks factor for Alzheimer’ s disease by modulating APOE expression. Objective: To measure the level of APOE expression in Alzheimer’ s disease. Methods: Brains were obtained at necropsy from 114 patients with early and late onset sporadic Alzheimer’ s disease in Gr eater Manchester (UK) during years 1986 to 2001. Total RNA was extracted from 84 brains. Purified lymphocytes were obtained from fresh blood from 16 probable Al zheimer cases from Lille (France). APOE and β - actin gene expression was dete rmined by reverse transcriptase polymerase chain reaction in brain and lymphocyt es. Results: An inverse correlation between APOE expression level and Aβ loads was observed. As previously described and extended to 114 cases here, an associ ation between the - 219 TT genotype and a higher level of parenchymal Aβ .depo sition was found, irrespective of APOE 4 allele status. This effect was more pronounced in older individuals, whereas higher Aβ load appeared more closely related to 4inthe younger age group (cut off point at the median age at death (7 2.5 years). The - 219 TT genotype was associated with a decrease in APOE expres sion. There was a 60% decrease in APOE expression in lymphocytes from probable Alzheimer cases v controls (p=0.01). Conclusions: In the oldest individuals, re duced APOE expression, modulated in part by - 219 G/T polymorphism, may influen ce risk and constitute a determinant Aβ load in Alzheimer’ s disease.
Background: It has been proposed that, independent of the 4 allele, APOE prom oter polymorphisms (- 491 A/T and 219 G/T) may be risks factor for Alzheimer’ s disease by modulating APOE expression. Objective: To measure the level of APOE expression in Alzheimer’ s disease. Methods: Brains were obtained at necropsy from 114 patients with early and late onset sporadic Alzheimer’ s disease in Gr eater Manchester (UK) during years 1986 to 2001. Total RNA was extracted from 84 brains. Purified lymphocytes were obtained from fresh blood from 16 probable Al zheimer cases from Lille (France). APOE and β - actin gene expression was dete rmined by reverse transcriptase polymerase chain reaction in brain and lymphocyt es. Results: An inverse correlation between APOE expression level and Aβ loads was observed. As previously described and extended to 114 cases here, an associ ation between the - 219 TT genotype and a higher level of parenchymal Aβ .depo sition was found, irrespective of APOE 4 allele status. This effect was more pronounced in older individuals, whereas higher Aβ load appeared more closely related to 4inthe younger age group (cut off point at the median age at death (7 2.5 years). The - 219 TT genotype was associated with a decrease in APOE expres sion. There was a 60% decrease in APOE expression in lymphocytes from probable Alzheimer cases v controls (p=0.01). Conclusions: In the oldest individuals, re duced APOE expression, modulated in part by - 219 G/T polymorphism, may influen ce risk and constitute a determinant Aβ load in Alzheimer’ s disease.
出处
《世界核心医学期刊文摘（神经病学分册）》
2005年第10期36-37,共2页
Digest of the World Core Medical Journals:Clinical Neurology
