This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (36)  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Alzheimer Disease  • Genetic Disorders  • Genetics, Other  • Alert me on articles by topic

Apolipoprotein E Genotype and Deposits of A40 and A42 in Alzheimer Disease

Megan J. McNamara, BS; Teresa Gomez-Isla, MD, PhD; Bradley T. Hyman, MD, PhD

Arch Neurol. 1998;55:1001-1004.

Objective  To examine the differential deposition of amyloid (A) peptide isoforms A40 and A42 in the Alzheimer disease (AD) brain in relation to the apolipoprotein E (APOE) genotype.

Background  The APOE 4 genotype is an inherited risk factor for AD and is associated with increased deposition of A protein in the cerebral cortex. Previous data from familial AD due to mutations in presenilin 1 and presenilin 2 genes and the amyloid precursor protein suggest that the long form of A peptide, A42, is selectively increased in these circumstances. Herein, we examine whether APOE genotype influenced the species of A peptide deposited.

Design and Methods  The amount of A40, A42, and total A deposited in immunostained temporal lobe tissue of 28 cases of AD of known APOE genotype was determined.

Results  Individuals with the APOE 4 genotype (APOE 4/4) were associated with both increased A40 (P<.05) and A42 (P<.05) compared with individuals without the APOE 4/4 genotype.

Conclusion  Our results differ from the data from AD due to mutations in presenilin 1 and presenilin 2 genes and the amyloid precursor protein and suggest that the APOE 4 genotype mediates increased A deposition by a mechanism that differs from that found in other genetic causes of AD.

From the Departments of Neurology, Massachusetts General Hospital, Boston (Ms McNamara and Dr Hyman) and the University of Minnesota, Minneapolis (Dr Gomez-Isla).

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Amyloid mediates the association of apolipoprotein E e4 allele to cognitive function in older people
Bennett et al.
J. Neurol. Neurosurg. Psychiatry 2005;76:1194-1199.
ABSTRACT | FULL TEXT  

Influence of the Apolipoprotein E Type 4 Allele on Cerebral Glucose Metabolism in Alzheimer's Disease Patients
Lee et al.
J. Neuropsychiatry Clin. Neurosi. 2003;15:78-83.
ABSTRACT | FULL TEXT  

Apolipoprotein E {epsilon}4 allele, AD pathology, and the clinical expression of Alzheimer's disease
Bennett et al.
Neurology 2003;60:246-252.
ABSTRACT | FULL TEXT  

Modulation of Alzheimer-Like Synaptic and Cholinergic Deficits in Transgenic Mice by Human Apolipoprotein E Depends on Isoform , Aging, and Overexpression of Amyloid beta Peptides But Not on Plaque Formation
Buttini et al.
J. Neurosci. 2002;22:10539-10548.
ABSTRACT | FULL TEXT  

Genetic and host factors for dementia in Down's syndrome
SCHUPF and Sergievsky
Br. J. Psychiatry 2002;180:405-410.
ABSTRACT | FULL TEXT  

Cerebrovascular and Brain Morphologic Correlates of Mild Cognitive Impairment in the National Heart, Lung, and Blood Institute Twin Study
DeCarli et al.
Arch Neurol 2001;58:643-647.
ABSTRACT | FULL TEXT  

The impact of different presenilin 1 andpresenilin 2 mutations on amyloid deposition, neurofibrillary changes and neuronal loss in the familial Alzheimer's disease brain: Evidence for other phenotype-modifying factors
Gomez-Isla et al.
Brain 1999;122:1709-1719.
ABSTRACT | FULL TEXT