Apolipoprotein E, memory and Alzheimer's disease

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Abstract

Apolipoprotein E (ApoE) ϵ4 is a well-documented risk factor for Alzheimer's disease (AD). Patients with AD show neuronal damage, particularly in the medial temporal lobe structures involved in memory processing. ApoE has been implicated in nerve regeneration following injury, and synaptogenesis in the hippocampus of experimental animals. Recent studies have shown an increased accumulation of βA4 amyloid and an increased deficit in ACh-containing neurons in the brains of AD patients that are homozygous for ApoE ϵ4 compared with those lacking ϵ4. Furthermore, AD patients with two ApoE ϵ4 alleles have more-severe loss in hippocampal volume in magnetic resonance imaging (MRI) scans, and more impairment in tests assessing delayed memory, than AD patients without the ϵ4 allele, in spite of similar global severity of dementia. Minor changes in hippocampal MRI volumetry can also be detected in nondemented elderly, particularly in those with an ϵ44 genotype. Data from a population-based study revealed that elderly subjects carrying the ϵ4 allele had worse learning ability than those with the ϵ22 or ϵ23 phenotypes, whereas these groups did not differ in other cognitive domains. These data suggest that ApoE ϵ4 might influence the magnitude of medial temporal lobe atrophy and memory impairment in AD and also in nondemented elderly. Trends Neurosci. (1996) 19, 224–228

Section snippets

Hippocampal volumes, memory and ApoE in AD patients

Lehtovirta and co-workers[10]tested the hypothesis that AD patients carrying the ϵ4 allele show more-severe hippocampal damage and memory impairment than AD patients without ϵ4. They studied 26 patients fulfilling the NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association) criteria for probable AD ([11]) and 16 age- and sex-matched controls. The AD patients were in the early stage of the disease.

The AD

Hippocampal volumes and ApoE in nondemented elderly

Another study was designed to test the hypothesis that nondemented elderly subjects carrying the ϵ4 allele have more-severe hippocampal atrophy than those without ϵ4. For this purpose, hippocampal volumes were measured on MRI scans acquired with the 1.5 T Magnetom in 32 healthy elderly individuals (22 women, 10 men, mean age of 69 ± 6 years)[12]. Of these, 16 fulfilled the criteria for age-associated memory impairment (AAMI)[13]and 16 had normal memory. None of the subjects fulfilled the

ApoE and memory in a population-based study

In the study mentioned above, the elderly individuals comprised a limited sample of the population. However, data from a population-based study supported these findings and showed that ApoE ϵ2 might be protective for learning and memory functions whereas ϵ4 seemed to be deleterious[14]. This study reported data from a random sample of 1300 subjects born in 1912–1921, drawn from the Kuopio population register in 1986. The population was investigated primarily for asymptomatic hyperglycemia and

ApoE and the deficit in ACh-containing neurons and ApoE in AD

A loss of choline acetyltransferase (ChAT) in the neocortex and hippocampus, and degeneration of the ACh-containing neurons in the nucleus basalis of Meynert are the most consistent neurochemical abnormalities in AD brain16, 17. To test the hypothesis that AD patients with two ϵ4 alleles have a more marked ChAT depletion than those without ϵ4, ChAT activities were measured post mortem in the frontal cortex of 32 AD patients with different ApoE genotypes[8]. The patients of this study were in a

Comments

Data are accumulating that ApoE genotype might be a major contributor to heterogeneity in AD (Table 1). Both in AD patients and in nondemented elderly subjects, memory functions and medial temporal lobe structures, such as the hippocampus, seem to be particularly vulnerable to deleterious effects of the ApoE ϵ4 allele. In contrast, the presence of the ApoE ϵ2 allele seemed to preserve learning ability in the elderly[14]. These data are in agreement with some very recent reports18, 19, 20, 21. A

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