Influence of the Apolipoprotein E Type 4 Allele on Cerebral Glucose Metabolism in Alzheimer's Disease Patients

Lee, Kang U.; Lee, Jae‐Shin; Kim, Ki Woo; Jhoo, Jin Hyeong; Lee, Dong Y.; Yoon, Jong Chul; Lee, Jung H.; Lee, Dong-Seon; Lee, Myung C.; Woo, Jong Inn

doi:10.1176/jnp.15.1.78

Cited by 10 publications

(12 citation statements)

References 38 publications

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“…However, a functional study [59] found a decreased glucose metabolism during a non-verbal memory task in non-symptomatic APOE 4 carriers compared to non-carriers at risk of AD (mean age 68 years) particularly in the left frontal and temporal lobes. Consequently, differences between groups (Lee et al [49] demonstrated their findings in very mild AD patients, while Hirono et al [50] studied early-and late-onset AD patients) might explain these divergent results.…”

Section: Discussionmentioning

confidence: 98%

“…An asymmetrical effect of the APOE genotype also appears to be present, although different studies report somewhat conflicting results with the 4 allele being associated with a significant decrease in glucose metabolism in the left inferior temporal lobe [49] , or a combination of decrease in the right temporal, frontal and occipital cortices and an increase in metabolism in the left temporal and parietal cortices [50] .…”

Section: Glucose Metabolismmentioning

confidence: 99%

“…However, 2 studies hint at the possibility that the APOE genotype might precipitate the disease but might not necessarily be involved in its later stages. Lee et al [49] found a decreased temporal glucose metabolism in mild AD sufferers but not in more severely affected groups, while Hirono et al [50] found an APOE effect in early-onset but not late-onset sufferers.…”

Section: Glucose Metabolismmentioning

confidence: 99%

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Neuroimaging and <i>APOE</i> Genotype: A Systematic Qualitative Review

Leach

Christensen

Anstey³

2007

Dement Geriatr Cogn Disord

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Apolipoprotein E (APOE) is the major genetic risk factor for late-onset Alzheimer’s disease (AD) and has also been implicated in cardiovascular disease, cognitive decline and cognitive changes in healthy ageing. The aim of this paper is to systematically review and critically assess the association between the APOE genotype and structural/functional cerebral changes as evidenced by brain imaging studies. A second aim is to determine whether these observed associations between APOE and the brain reflect changes which are consistent with the progression of AD neurodegenerative changes described in Braak stages. A search of Pubmed, Psycinfo, and Web of Science databases identified 64 articles available for qualitative review. The review found that presence of the APOE Ε4 allele is associated with (1) hippocampal, amygdalar and entorhinal cortex atrophy, (2) increased brain atrophy, (3) increased white matter hyperintensity volumes and (4) altered cerebral blood flow and glucose metabolism patterns. It is possible that there are critical age ranges when these effects are evident and that the APOE Ε2 genotype might present a risk. We conclude that structural brain change is associated with the APOE genotype and that it is more salient in younger ageing individuals.

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Section: Discussionmentioning

confidence: 98%

Section: Glucose Metabolismmentioning

confidence: 99%

Section: Glucose Metabolismmentioning

confidence: 99%

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Neuroimaging and <i>APOE</i> Genotype: A Systematic Qualitative Review

Leach

Christensen

Anstey³

2007

Dement Geriatr Cogn Disord

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“…The mechanism by which APOE*4 participates in AD pathogenesis is not known. However, APOE*4 gene dose is known to be a major risk factor for late onset AD (35). Six peptides were identified for this protein.…”

Section: Discussionmentioning

confidence: 99%

Proteomics Identification of Proteins in Human Cortex Using Multidimensional Separations and MALDI Tandem Mass Spectrometer

Pan

Shi

Jin

et al. 2007

Molecular & Cellular Proteomics

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It is essential to characterize the proteome of various regions of human brain because most, if not all, neurodegenerative diseases are region-specific. Here we report an in-depth proteomics identification of proteins extracted from the frontal cortex, a region playing a critical role in cognitive function. The integrated proteomics analytical flow consisted of biochemical fractionation, strong cation exchange chromatography, reverse phase liquid chromatography, and MALDI-TOF/TOF mass spectrometric analysis. In total, 812 proteins were confidently identified with two or more peptides. These proteins demonstrated diverse isoelectric points and molecular weights and are involved in several molecular functions, including protein binding, catalytic activity, transport, structure, and signal transduction. A number of proteins known to be associated with neurodegenerative diseases were also identified. Detailed characterization of these proteins will supply the necessary information to appropriately interpret proteins associated with aging and/or age-related neurodegenerative diseases. Finally 140 proteins found in the cortical proteome were present in the proteome of cerebrospinal fluid, providing tissue-specific candidates for biomarker discovery in body fluid.

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“…Neuroimaging studies may shed additional light on the association between ApoE e4 and psychotic manifestations of AD. One in vivo SPECT study has suggested that delusions in AD may be associated with hypoperfusion in the temporal lobes (Starkstein et al, 1994), and some (Lee et al, 2003) but not all (van Dyck et al, 1998) functional imaging studies have shown that AD patients who carry the e4 allele have reduced temporal lobe function. The structural MRI literature is more unified in showing greater medial temporal lobe atrophy in association with the e4 allele in AD (Lehtovirta et al, 1996b;Hashimoto et al, 2001;Basso et al, in press).…”

Section: Interpretation Of An Increased Risk Of Psychosis In Apoe E4 mentioning

confidence: 99%

Apolipoprotein E ɛ4 Allele Increases Risk for Psychotic Symptoms in Alzheimer's Disease

Zdanys

Kleiman

MacAvoy

et al. 2006

Neuropsychopharmacol

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The apolipoprotein E (ApoE) e4 allele is a well-documented genetic risk factor for sporadic Alzheimer's disease (AD). Its association with psychopathology among AD patients has been the subject of discrepant reports. We aimed to determine whether ApoE e4 + and e4-AD patients exhibit a different risk profile for psychotic symptoms and other behavioral disturbances. The Neuropsychiatric Inventory (NPI) was administered to determine the frequency and severity of psychotic and other behavioral symptoms in a sample of n ¼ 266 AD patients who had been genotyped for ApoE. Multiple logistic regression models were used to calculate the association between the ApoE e4 allele and the presence of psychotic symptoms (delusions or hallucinations). Exploratory analyses were also conducted to determine the impact of disease severity on e4 effects and to examine the association between e4 and other behavioral symptoms. ApoE e4 was significantly associated with psychotic symptoms (odds ratio (OR) ¼ 1.87, 95% CI ¼ 1.07-3.29, P ¼ 0.029), adjusting for age, sex, education, and MMSE score. More stringent definitions of clinically significant psychosis yielded similar results. Exploratory analyses suggested that this effect accrued specifically from patients with severe-stage AD and primarily from an association between e4 and delusions. The e4 allele did not appear to influence the development of most other behavioral symptoms in our sample. In conclusion, AD patients who carry the ApoE e4 allele are at greater risk than noncarriers for developing psychotic symptoms, particularly as the severity of their dementia progresses.

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Influence of the Apolipoprotein E Type 4 Allele on Cerebral Glucose Metabolism in Alzheimer's Disease Patients

Cited by 10 publications

References 38 publications

Neuroimaging and <i>APOE</i> Genotype: A Systematic Qualitative Review

Neuroimaging and <i>APOE</i> Genotype: A Systematic Qualitative Review

Proteomics Identification of Proteins in Human Cortex Using Multidimensional Separations and MALDI Tandem Mass Spectrometer

Apolipoprotein E ɛ4 Allele Increases Risk for Psychotic Symptoms in Alzheimer's Disease

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