Volumes of hippocampus, amygdala and frontal lobe in Alzheimer patients with different apolipoprotein E genotypes

doi:10.1016/0306-4522(95)00014-A

Neuroscience

Volume 67, Issue 1, July 1995, Pages 65-72

https://doi.org/10.1016/0306-4522(95)00014-A Get rights and content

Abstract

An increased frequency of apolipoprotein E E4 allele has been reported in patients with late onset Alzheimer's disease. Apolipoprotein E participates in the transport of cholesterol and other lipids and interferes with the growth and regeneration of both peripheral and central nervous system tissues during development and after injury. Apolipoprotein E is also implicated in synaptogenesis. Apolipoprotein E isoforms differ in binding to amyloid-β-protein and tau proteinin vitro. Here, we wanted to study the effect of apolipoprotein E genotype on the magnitude of damage in the hippocampus, where a marked synapse loss exists in Alzheimer's disease. We measured by magnetic resonance imaging the volumes of the hippocampus, amygdala, and frontal lobes in the three Alzheimer subgroups: patients with 2, 1 or 0 E4 alleles. We also investigated the profile of deficits on tests assessing memory, language, visuospitial, executive, and praxic functions of these Alzheimer subgroups. All Alzheimer patients were at early stage of the disease. We found that Alzheimer patients with E4/4 genotype (N = 5) had smaller volumes of the hippocampus and the amygdala than those with E3/4 (N = 9) and those with E3/3 or E2/3 (N = 12). The difference was significant for the right hippocampus (−54% of control) and the right amygdala (−37% of control). The volumes of the frontal lobes were similar across the Alzheimer subgroups. The patients with E4/4 also showed lowest scores on delayed memory tests and differed from E3/3, 3/2 patients in the list learning test (<0.05). The Alzheimer subgroups did not differ in age, age at onset, the global clinical severity of dementia or in the profile of other neurophyschological deficits.

The results suggest that Alzheimer patients with apolipoprotein E E4/4 genotype have severe damage of the hippocampus and amygdala very early in the disease process and differ from Alzheimer patients accumulation of the amyloid and paired helical filaments or greater loss of synapses in E4 homozygous Alzheimer patients, is of interest and worth studying.

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Human apolipoprotein E (apoE) ε4 remains the most important genetic risk factor for late onset AD. ApoE4 subjects in various age brackets also have smaller hippocampal volume and this applies to both AD (Lehtovirta et al., 1995; Pievani et al., 2011) and healthy subjects (Burggren et al., 2008; O’Dwyer et al., 2012), and particularly to healthy women (Cohen, Small, Lalonde, Friz, & Sunderland, 2001) as well as women with MCI (Fleisher et al., 2005). Furthermore, the APOEε4 gene is associated with enhanced longitudinal hippocampal volume loss (Jak, Houston, Nagel, Corey-Bloom, & Bondi, 2007; Moffat, Szekely, Zonderman, Kabani, & Resnick, 2000) and whole brain atrophy rates are positively correlated with APOEε4 gene-dose in late middle-aged individuals (Chen et al., 2007).
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Volumes of hippocampus, amygdala and frontal lobe in Alzheimer patients with different apolipoprotein E genotypes

Abstract

Neuropsychologia

J. Psychiat. Res.

Neurobiol. Aging

Brain Res.

Cortex

Lancet

Molec. Brain Res.

Neuroscience

Lancet

Brain Res.

Lancet

Exp. Neurol.

A synaptic model of memory: long-term potentiation in the hippocampus

Nature

Tetrahydroaminoacridine and Alzheimer's disease. For the few, but we don't know which few

Br. Med. J.

Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families

Science

Amygdala atrophy in Alzheimer's disease. Anin vitro magnetic resonance imaging study

Arch. Neurol.

Structure of the Human Brain. A Photographic Atlas

Neuropathological changes in scrapie and Alzheimer's disease are associated with increased expression of apolipoprotein E and cathepsin D in astrocytes

J. Virol.

The Human Hippocampus. An Atlas of Applied Anatomy

Apolipoprotein E polymorphism in the Finnish population: gene frequencies and relation to lipoprotein concentration

J. Lipid Res.

The Assessment of Aphasia and Related Disorders

The apolipoprotein E polymorphism: a comparison of allele frequencies and effects in nine populations

Am. J. Hum. Genet.

A rating scale for depression

J. Neurol. Neurosurg. Psychiat.

Recall and recognition memory in patients with Alzheimer's and Parkinson's diseases

Ann. Neurol.

Restriction isotyping of human apolipoprotein E by gene amplication and cleavage with HhaI

J. Lipid Res.

MR-based hippocampal volumetry in the diagnisis of Alzheimer's disease

Neurology

The Boston Naming Test

Quantification of magnetic resonance scans for hippocampal and parahippocampal atrophy in Alzheimer's disease

Neurology