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APOE and Alzheimer's-disease story becomes more complicated
SCIENCE AND MEDICINE
NEWS
Oestrogen helps to protect memory into old age the memory test twice: once before score of zero and points are added for they had begun ERT omissions, additions, and then again some distortions, and years later after other errors. ERT. These women In Resnick’s study, were matched with 116 women were 18 women who also receiving ERT at the had taken the test time of the test, while twice but who had 172 had never taken never taken ERT. ERT. Resnick and During an average her colleagues found interval between tests that, after correction of 6 years, the error for age, the women Helping our memory in later life rate among the who were receiving women who had begun ERT ERT scored significantly better than remained stable, while the error rate “never-treated” women; the scores of among the never-treated women rose the two groups differed by about oneon average by 2 points. By compariquarter of a standard deviation. son, a separate study looking at The researchers then looked at a BVRT scores as a predictor of subgroup of women who had taken Alzheimer’s-disease risk found a Many US women doctors choose hormone replacement therapy 6-point difference in the change of 47·4% of postmenopausal women doctors surveyed in a US study say they use scores over a 6-year interval between hormone replacement therapy (HRT). This compares with only 24% of normal patients and those who would postmenopausal women using HRT nationally in the USA. The results on women later develop Alzheimer’s disease. physicians come from the responses of 1466 women surveyed as part of the Resnick and co-workers conclude Women Physicians’ Health Study (Ann Intern Med 1997; 127: 1093–96). that their new findings, as well as Physicians often adopt new health behaviours earlier than society as a whole, those of other studies, “suggest that note the researchers, so “higher rates of HRT use by women physicians and early therapeutic interventions can other well-educated women may presage greater use of HRT for US women in impact age-associated declines in the future”. Sally McNagny et al (Emory University School of Medicine, Atlanta, cognition and memory, and the GA, USA) also report that younger women physicians are more likely to use development of dementing illness”.
estrogen replacement therapy (ERT) may help to reduce ageassociated memory loss, according to a study published recently in Neurology (1997; 49: 1491–97). The study consisted of two parts, explains lead author Susan Resnick of the US National Institute of Aging’s Laboratory of Personality and Cognition (Baltimore, MD). In the first part, 288 postmenopausal women, all participants in the Baltimore Longitudinal Study of Aging, were given a test of visual memory called the Benton Visual Retention Test (BVRT). In this test, individuals are shown designs for 10 seconds and then asked to draw them from memory. Perfect reproductions are given a
Bubbles
O
HRT. 59·8% of 40–49 year-olds do so, but only 36·5% of 60–70 year-olds. Michael McCarthy
APOE and Alzheimer’s-disease story becomes more complicated he association between the 4 allele of the apolipoprotein-E gene (APOE) and an increased risk of developing Alzheimer’s disease (AD) is well known. But now, researchers from Spain and the USA reveal that a genetic polymorphism in the transcriptional regulation region of APOE may also be linked with AD risk. Their results provide new insight into the disease process and may help in the search for therapeutic drug targets. Fernando Valdivieso from the Universidad Autonoma de Madrid (Madrid, Spain), Alison Goate from Washington University School of Medicine (St Louis, MO, USA)
T
THE LANCET • Vol 351 • January 3, 1998
and their colleagues studied an A/T polymorphism at position -491 of the APOE transcriptional regulatory unit in two populations of European descent (Spanish and North American). In each of the case-control clinical populations, the -491 AA genotype was associated with an increased risk for AD when compared with the AT and TT genotypes combined. In the Spanish population, the increased risk was more than three-fold, but the association was weaker for the US population (OR 1·81). The association of -491 AA with AD was independent of APOE4 status (Nat Genet 1998; 18: 69–71).
The researchers report that, invitro, the -491A allele is associated with higher constitutive APOE transcription. Recent mouse-model data, notes Goate, have shown that -amyloid deposition correlates with APOE expression. Although apolipoprotein E in the cerebrospinal fluid is thought to protect neuronal cells from -amyloid peptides, increased amounts of the protein are cytotoxic. Taken together, “these results suggest that higher amounts of apolipoprotein A might lead to cell death and to more -amyloid deposition”, says Goate. Jane Bradbury
39
NEWS
Oestrogen helps to protect memory into old age the memory test twice: once before score of zero and points are added for they had begun ERT omissions, additions, and then again some distortions, and years later after other errors. ERT. These women In Resnick’s study, were matched with 116 women were 18 women who also receiving ERT at the had taken the test time of the test, while twice but who had 172 had never taken never taken ERT. ERT. Resnick and During an average her colleagues found interval between tests that, after correction of 6 years, the error for age, the women Helping our memory in later life rate among the who were receiving women who had begun ERT ERT scored significantly better than remained stable, while the error rate “never-treated” women; the scores of among the never-treated women rose the two groups differed by about oneon average by 2 points. By compariquarter of a standard deviation. son, a separate study looking at The researchers then looked at a BVRT scores as a predictor of subgroup of women who had taken Alzheimer’s-disease risk found a Many US women doctors choose hormone replacement therapy 6-point difference in the change of 47·4% of postmenopausal women doctors surveyed in a US study say they use scores over a 6-year interval between hormone replacement therapy (HRT). This compares with only 24% of normal patients and those who would postmenopausal women using HRT nationally in the USA. The results on women later develop Alzheimer’s disease. physicians come from the responses of 1466 women surveyed as part of the Resnick and co-workers conclude Women Physicians’ Health Study (Ann Intern Med 1997; 127: 1093–96). that their new findings, as well as Physicians often adopt new health behaviours earlier than society as a whole, those of other studies, “suggest that note the researchers, so “higher rates of HRT use by women physicians and early therapeutic interventions can other well-educated women may presage greater use of HRT for US women in impact age-associated declines in the future”. Sally McNagny et al (Emory University School of Medicine, Atlanta, cognition and memory, and the GA, USA) also report that younger women physicians are more likely to use development of dementing illness”.
estrogen replacement therapy (ERT) may help to reduce ageassociated memory loss, according to a study published recently in Neurology (1997; 49: 1491–97). The study consisted of two parts, explains lead author Susan Resnick of the US National Institute of Aging’s Laboratory of Personality and Cognition (Baltimore, MD). In the first part, 288 postmenopausal women, all participants in the Baltimore Longitudinal Study of Aging, were given a test of visual memory called the Benton Visual Retention Test (BVRT). In this test, individuals are shown designs for 10 seconds and then asked to draw them from memory. Perfect reproductions are given a
Bubbles
O
HRT. 59·8% of 40–49 year-olds do so, but only 36·5% of 60–70 year-olds. Michael McCarthy
APOE and Alzheimer’s-disease story becomes more complicated he association between the 4 allele of the apolipoprotein-E gene (APOE) and an increased risk of developing Alzheimer’s disease (AD) is well known. But now, researchers from Spain and the USA reveal that a genetic polymorphism in the transcriptional regulation region of APOE may also be linked with AD risk. Their results provide new insight into the disease process and may help in the search for therapeutic drug targets. Fernando Valdivieso from the Universidad Autonoma de Madrid (Madrid, Spain), Alison Goate from Washington University School of Medicine (St Louis, MO, USA)
T
THE LANCET • Vol 351 • January 3, 1998
and their colleagues studied an A/T polymorphism at position -491 of the APOE transcriptional regulatory unit in two populations of European descent (Spanish and North American). In each of the case-control clinical populations, the -491 AA genotype was associated with an increased risk for AD when compared with the AT and TT genotypes combined. In the Spanish population, the increased risk was more than three-fold, but the association was weaker for the US population (OR 1·81). The association of -491 AA with AD was independent of APOE4 status (Nat Genet 1998; 18: 69–71).
The researchers report that, invitro, the -491A allele is associated with higher constitutive APOE transcription. Recent mouse-model data, notes Goate, have shown that -amyloid deposition correlates with APOE expression. Although apolipoprotein E in the cerebrospinal fluid is thought to protect neuronal cells from -amyloid peptides, increased amounts of the protein are cytotoxic. Taken together, “these results suggest that higher amounts of apolipoprotein A might lead to cell death and to more -amyloid deposition”, says Goate. Jane Bradbury
39