close

Вход

Забыли?

вход по аккаунту

?

Apolipoprotein E4 Phenotype in patients with Alzheimer's disease.

код для вставкиСкачать
LETTERS
Apolipoprotein E4:
Phenotype in Patients with
Alzheimer’s Disease
Distribution of Patients and Controh According to the
Apohpopvotein Phenotype (2t a t )
F. Mahieux, MD, R. Couderc, PhD, A. Moulignier, MD,
S. Bailleul, PhD, N. Podrabinek, MD, and J. Laudet, M D
Healthy blood
donors (3)
n (%)
The study of Mayeux and co-workers 11) confirmed the initial work of Saundurs and colleagues 121 of an abnormal repartition of apolipoprotein E (apoE) genotypes in Alzheimer’s disease (AD). Moreover, its original design brings
interesting new data on the following two facts: ( 1 ) The frequency of apoE-~4genotype may vary among different ethnic
groups, and (2) the association between apoE-c4 gene and
A D may be found regardless of the age of onset of the disease. All previous works used an amplification and restriction
isotyping method to determine the apoE genotype.
W e recently developed a far simpler method for determining the protein phenotype, by direct plasma isoelectrofocusing {3j. We have established the apoE phenotype in 76 patients meeting criteria for probable (n = 50) or possible (n
= 26) AD, ambulatory [ A ) or resident in a long-stay hospital
(mean age = 78.4 yr; range = 59-93 yr; sex = 71%
women). Seven patients (9.2%) had a presenile onset (<65
yr). The distribution of the apoE4 phenotype was highly different between the patients who had at least one €4allele (n
= 33) (Table) and the general population (evaluated from
498 healthy young blood donors 131) (43.45% vs 22.6%; x’
test:p < 0.001, odds ratio = 2.7).Homozygotes represented
10.5% of the patients, compared with 1.5% in the general
pdpulation ( p < 0.001, odds ratio = 8.3). There was no
significant difference in the ratio of possible to probable AD
between the patients with and without the E4 isoform. The
frequency of presenile onset was similar regardless of the
apoE phenotype.
W e would like to emphasize four points. First, our results
are in full agreement with those of Mayeux and colleagues
on the age of onset. Second, the use of aged controls may
lead to a considerable bias, according to the well-known vascular risk linked with the apoE-~2and €4 genes, as we already
observed in a previous study in cerebrovascular disease [S].
Thus, it would be preferable to use young people as a control
population that would better reflect the general population
frequency of apoE genotypes. Third, the apoE4 phenotype
frequency is as high in possible as in probable AD. Fourth,
the advantage of phenotypic detection is that it can be done
in any hospital laboratory. We consider that the apoE phenotype should now be determined as part of the workup for
possible and probable AD. Homozygosity 414 appears to be
a fully diagnostic element in dementia of undetermined type
and could be added to the National Institute of Neurological
and Communicative Disorders and Stroke-Alzheimer’s Disease and Related Disorders Association criteria for probable
AD.
Consultation me‘moirr and Sewice de Biochimie
Hopital Tenon
Semiice de givontologie
Hopital Vaugirard
Paris. France
Subjects
414
7
(1.5)
Other
314 or 214 Phenotypes p
105
(21.1)
386
(77.5)
0.001
8
(10.5)
4
(8 0)
4
11 (rc)
(15.4)
Presenile onset
I
(12.5)
Ischemic cerebro- 1
vascular disease
(%)
(n = 69)
Aged controls
0
(n = 6 8 ) (o/o
Patients
n (9%)
Probable A D
n (57)
Possible A D
25
(32.9)
16
(32.0)
43
(56.0)
22
9
(34.6)
11
(42.3)
4
(9.3)
58
2
(8)
10
(1.4)
9
(13.2)
(44)
(14.5)
59
(86.8)
NS
(84.0)
Mean age at onset ( I test) and family history of dementla for each
patient subgroup (x’test).
AD
=
Alzheimer’s disease.
References
1. Mayeux R, Stern Y ,Ottman R, er al. The apolipoprotein €4 allele
in patients with Alzheimer’s diseue. Ann Neurol 1993;34:752-
7 54
2. Saunders AM, Strittmatter WJ, Schmechel DE, et al. Association
of apolipoprotein E allele €4with late-onset familial and sporadic
Alzheimer’s disease. Neurology 19%;43: 1467-147 2
3 . Bailleul S, Couderc R, Landais V, et al. Direct phenocyping of
human apolipoprotein E in plasma: application to population frequency distribution in Paris (France). Hum Hered 1993;43:159I65
4. Mahiew F, Moulignier A, Michelet D, et al. Consultation sp&
cialiske d e la memoire. Intkr@te t bilan de 2 annbes de fonctionnement. Presse Med 1993;22:617-621
5 . Couderc R, Mahiew F, Bailleul S, ec al. Apolipoprotein E phenotypes in ischemic cerebrovascular disease. A case control study.
Stroke 1991;24:661-664
Reply
Richard Mayeux, MD, MSE, and Ben Tycko, MD, PhD
We thank Mahiew and colleagues for their comments, and
for adding their data to those of others confirming the relationship between apolipoprotein-a4 and Alzheimer’s disease
[ 1-31, Because the use of apolipoprotein-e genotypes (and
pouiblji phenotypes) is likely to expand in the research of Alzheimer’s disease, simpler methods would be desirable. However, issues such as reliability, validity, feasibility, time, efficiency, and cost also need to be compared. How does the
method of direct plasma isoelectrofocusing compare with
polymerase chain reaction amplification and restriction site
analysis with regard to these issues? Does one method have
a distinct advantage over the other? If a laboratory is using
506 Copyright 0 1994 by the American Neurological Association
Документ
Категория
Без категории
Просмотров
3
Размер файла
125 Кб
Теги
patients, phenotypic, apolipoprotein, disease, alzheimers
1/--страниц
Пожаловаться на содержимое документа