General Information:

Id: 7,848
Diseases: Alzheimer disease - [OMIM]
Homo sapiens
fresh frozen brain tissue blocks of middle frontal gyrus (MFG), middle temporal gyrus (MTG), and cerebellum were obtained from normal subjects and cases of definite AD diagnosed according to CERAD criteria
article
Reference: Bandaru VV et al.(2009) ApoE4 disrupts sterol and sphingolipid metabolism in Alzheimers but not normal brain Neurobiol. Aging 30: 591-599 [PMID: 17888544]

Interaction Information:

Comment The epsilon 4 allele of ApoE is associated with an earlier onset and faster progression of Alzheimer's disease in patients with the familial form of this neurodegenerative condition. ApoE4 disrupts sterol and sphingolipid metabolism in Alzheimer's but not normal brain.
Formal Description
Interaction-ID: 78037

gene/protein mutant

APOE (isoform E4)

increases_activity of

Comment The epsilon 4 allele of ApoE is associated with an earlier onset and faster progression of Alzheimer's disease in patients with the familial form of this neurodegenerative condition. ApoE4 disrupts sterol and sphingolipid metabolism in Alzheimer's but not normal brain.
Formal Description
Interaction-ID: 78301

gene/protein mutant

APOE (isoform E4)

decreases_activity of

in AD but not normal brain
Comment The epsilon 4 allele of ApoE is associated with an earlier onset and faster progression of Alzheimer's disease in patients with the familial form of this neurodegenerative condition. ApoE4 disrupts sterol and sphingolipid metabolism in Alzheimer's but not normal brain.
Formal Description
Interaction-ID: 78302

gene/protein mutant

APOE (isoform E4)

decreases_activity of

in AD but not normal brain
Comment Changes of sphingolipid and sterol levels (without regard to the patients’ ApoE genotype) in the middle frontal gyrus (MFG) of AD patients compared with those of neurologically normal subjects were found. In the MFG grey matter, significant increases of sphingomyelin C16:0, C18:0, C22:0 and C24:0, steraoyl, cholesterol, and the cholesterol ester C18:1 (range 1.8- to 4.9-fold) were found.
Formal Description
Interaction-ID: 78303

increases_quantity of

drug/chemical compound

SM C16:0

in the middle frontal gyrus grey matter of AD patients compared to normal subjects; (1.8-fold increase)
Comment Changes of sphingolipid and sterol levels (without regard to the patients’ ApoE genotype) in the middle frontal gyrus (MFG) of AD patients compared with those of neurologically normal subjects were found. In the MFG grey matter, significant increases of sphingomyelin C16:0, C18:0, C22:0 and C24:0, steraoyl, cholesterol, and the cholesterol ester C18:1 (range 1.8- to 4.9-fold) were found.
Formal Description
Interaction-ID: 78305

increases_quantity of

drug/chemical compound

SM C18:0

in the middle frontal gyrus grey matter of AD patients compared to normal subjects; (4.9-fold increase)
Comment Changes of sphingolipid and sterol levels (without regard to the patients’ ApoE genotype) in the middle frontal gyrus (MFG) of AD patients compared with those of neurologically normal subjects were found. In the MFG grey matter, significant increases of sphingomyelin C16:0, C18:0, C22:0 and C24:0, steraoyl, cholesterol, and the cholesterol ester C18:1 (range 1.8- to 4.9-fold) were found.
Formal Description
Interaction-ID: 78306

increases_quantity of

drug/chemical compound

SM C22:0

in the middle frontal gyrus grey matter of AD patients compared to normal subjects; (4.4-fold increase)
Comment Changes of sphingolipid and sterol levels (without regard to the patients’ ApoE genotype) in the middle frontal gyrus (MFG) of AD patients compared with those of neurologically normal subjects were found. In the MFG grey matter, significant increases of sphingomyelin C16:0, C18:0, C22:0 and C24:0, steraoyl, cholesterol, and the cholesterol ester C18:1 (range 1.8- to 4.9-fold) were found.
Formal Description
Interaction-ID: 78307

increases_quantity of

drug/chemical compound

SM C24:0

in the middle frontal gyrus grey matter of AD patients compared to normal subjects; (2.4-fold increase)
Comment Changes of sphingolipid and sterol levels (without regard to the patients’ ApoE genotype) in the middle frontal gyrus (MFG) of AD patients compared with those of neurologically normal subjects were found. In the MFG grey matter, significant increases of sphingomyelin C16:0, C18:0, C22:0 and C24:0, steraoyl, cholesterol, and the cholesterol ester C18:1 (range 1.8- to 4.9-fold) were found.
Formal Description
Interaction-ID: 78308

increases_quantity of

drug/chemical compound

Steraoyl

in the middle frontal gyrus grey matter of AD patients compared to normal subjects
Comment Changes of sphingolipid and sterol levels (without regard to the patients’ ApoE genotype) in the middle frontal gyrus (MFG) of AD patients compared with those of neurologically normal subjects were found. In the MFG grey matter, significant increases of sphingomyelin C16:0, C18:0, C22:0 and C24:0, steraoyl, cholesterol, and the cholesterol ester C18:1 (range 1.8- to 4.9-fold) were found.
Formal Description
Interaction-ID: 78309

increases_quantity of

drug/chemical compound

Cholesterol

in the middle frontal gyrus grey matter of AD patients compared to normal subjects
Drugbank entries Show/Hide entries for
Comment Changes of sphingolipid and sterol levels (without regard to the patients’ ApoE genotype) in the middle frontal gyrus (MFG) of AD patients compared with those of neurologically normal subjects were found. In the MFG grey matter, significant increases of sphingomyelin C16:0, C18:0, C22:0 and C24:0, steraoyl, cholesterol, and the cholesterol ester C18:1 (range 1.8- to 4.9-fold) were found.
Formal Description
Interaction-ID: 78310

increases_quantity of

drug/chemical compound

Cholesterol ester C18:1

in the middle frontal gyrus grey matter of AD patients compared to normal subjects
Comment In MFG white matter, no difference between sphingomyelin and sterol levels between AD and normal subjects, but significant decreases of ceramide C16:0, C22:0, C24:1, steraoyl, and sulfatide (range 3.7- to 9.2-fold) were found.
Formal Description
Interaction-ID: 78311

NOT affects_quantity of

drug/chemical compound

Sphingomyelin

in the middle frontal gyrus white matter of AD patients compared to normal subjects
Comment In MFG white matter, no difference between sphingomyelin and sterol levels between AD and normal subjects, but significant decreases of ceramide C16:0, C22:0, C24:1, steraoyl, and sulfatide (range 3.7- to 9.2-fold) were found.
Formal Description
Interaction-ID: 78312

NOT affects_quantity of

drug/chemical compound

Sterol

in the middle frontal gyrus white matter of AD patients compared to normal subjects
Comment In MFG white matter, no difference between sphingomyelin and sterol levels between AD and normal subjects, but significant decreases of ceramide C16:0, C22:0, C24:1, steraoyl, and sulfatide (range 3.7- to 9.2-fold) were found.
Formal Description
Interaction-ID: 78316

decreases_quantity of

drug/chemical compound

Ceramide C16:0

in the middle frontal gyrus white matter of AD patients compared to normal subjects; (3.7-fold decrease)
Comment In MFG white matter, no difference between sphingomyelin and sterol levels between AD and normal subjects, but significant decreases of ceramide C16:0, C22:0, C24:1, steraoyl, and sulfatide (range 3.7- to 9.2-fold) were found.
Formal Description
Interaction-ID: 78318

decreases_quantity of

drug/chemical compound

Ceramide C22:0

in the middle frontal gyrus white matter of AD patients compared to normal subjects; (4.5-fold decrease)
Comment In MFG white matter, no difference between sphingomyelin and sterol levels between AD and normal subjects, but significant decreases of ceramide C16:0, C22:0, C24:1, steraoyl, and sulfatide (range 3.7- to 9.2-fold) were found.
Formal Description
Interaction-ID: 78319

decreases_quantity of

drug/chemical compound

Ceramide C24:1

in the middle frontal gyrus white matter of AD patients compared to normal subjects; (9.2-fold decrease)
Comment In MFG white matter, no difference between sphingomyelin and sterol levels between AD and normal subjects, but significant decreases of ceramide C16:0, C22:0, C24:1, steraoyl, and sulfatide (range 3.7- to 9.2-fold) were found.
Formal Description
Interaction-ID: 78323

decreases_quantity of

drug/chemical compound

Steraoyl

in the middle frontal gyrus white matter of AD patients compared to normal subjects; (8.4-fold decrease)
Comment In MFG white matter, no difference between sphingomyelin and sterol levels between AD and normal subjects, but significant decreases of ceramide C16:0, C22:0, C24:1, steraoyl, and sulfatide (range 3.7- to 9.2-fold) were found.
Formal Description
Interaction-ID: 78324

decreases_quantity of

drug/chemical compound

Sulfatide

in the middle frontal gyrus white matter of AD patients compared to normal subjects; (4.4-fold decrease)
Comment The data indicate that in the MFG (middle frontal gyrus), ceramide and sterol levels were increased in the cell bodies (grey matter) and ceramide was decreased in the fiber tracks (white matter) of AD brain compared with similar tissues from normal subjects.
Formal Description
Interaction-ID: 78325

affects_activity of

tissue/cell line

cerebral gray matter

Comment The data indicate that in the MFG (middle frontal gyrus), ceramide and sterol levels were increased in the cell bodies (grey matter) and ceramide was decreased in the fiber tracks (white matter) of AD brain compared with similar tissues from normal subjects.
Formal Description
Interaction-ID: 78326

affects_activity of

tissue/cell line

cerebral white matter

Comment In the MFG grey matter of AD patients with an ApoE4 genotype, there were increased levels of cholesterol, and the cholesterol esters C16:0, and C18:1 (range 2.6- to 3.4-fold).
Formal Description
Interaction-ID: 78329

gene/protein mutant

APOE (isoform E4)

increases_quantity of

drug/chemical compound

Cholesterol

in the MFG (middle frontal gyrus) grey matter of AD patients (in the cell bodies but not in the fiber tracks); compared with AD patients expressing ApoE3
Drugbank entries Show/Hide entries for
Comment Hypothesis: ApoE4 may disrupt brain sterol metabolism only in the setting of a neurodegenerative condition.
Formal Description
Interaction-ID: 78331

none selected

Drugbank entries Show/Hide entries for or
Comment In the MFG grey matter, there were significant decreases of sphingomyelin C22:0 (12.5-fold), and C24:0 (6.2-fold), and significant increases of ceramide C18:0 (2.0-fold) and C24:1 (1.8-fold) in ApoE4 compared with ApoE3 AD brain.
Formal Description
Interaction-ID: 78335

gene/protein mutant

APOE (isoform E4)

decreases_quantity of

drug/chemical compound

SM C22:0

in the MFG grey matter in ApoE4 compared with ApoE3 AD brain; (12.5-fold decrease)
Comment In the MFG white matter, while there were no significant differences in sphingomeylin, there were significant differences in ceramide C22:0 (2.6-fold increase), C24:0 (1.2-fold decrease), and sulfatide (1.7-fold increase), in ApoE4 vs. ApoE3 brain.
Formal Description
Interaction-ID: 78337

gene/protein mutant

APOE (isoform E4)

increases_quantity of

drug/chemical compound

Ceramide C22:0

in the MFG white matter in ApoE4 vs. ApoE3 brain; (2.6-fold increase)
Comment In the MFG grey matter there was a significant increase in the lysine adduct of 4-HNE (4.9-fold) and, no significant difference in MFG white matter content of ApoE4 compared with ApoE3 AD brain.
Formal Description
Interaction-ID: 78338

gene/protein mutant

APOE (isoform E4)

increases_quantity of

drug/chemical compound

4-Hydroxynonenal

in the MFG grey matter of ApoE4 compared with ApoE3 AD brain; (4.9-fold increase)
Comment Ceramides C18:0, C24:1 and sulfatide were increased in the MFG (middle frontal gyrus) grey matter of ApoE4 AD patients (1.8- to 2.0-fold).
Formal Description
Interaction-ID: 78339

gene/protein mutant

APOE (isoform E4)

increases_quantity of

drug/chemical compound

Ceramide C18:0

in the MFG grey matter of ApoE4 AD patients
Comment In the MTG (middle temporal gyrus) grey matter, only the cholesterol ester C18:1 was elevated (2.4-fold) in AD patients expressing ApoE4 compared with AD patients expressing ApoE3.
Formal Description
Interaction-ID: 78369

gene/protein mutant

APOE (isoform E4)

increases_quantity of

drug/chemical compound

Cholesterol ester C18:1

in the MTG (middle temporal gyrus) grey matter in AD patients expressing ApoE4, (in the cell bodies but not in the fiber tracks); (2.4-fold increase), compared with AD patients expressing ApoE3
Comment In the MFG grey matter of AD patients with an ApoE4 genotype, there were increased levels of cholesterol, and the cholesterol esters C16:0, and C18:1 (range 2.6- to 3.4-fold).
Formal Description
Interaction-ID: 78370

gene/protein mutant

APOE (isoform E4)

increases_quantity of

drug/chemical compound

Cholesterol ester C16:0

in the MFG (middle frontal gyrus) grey matter of AD patients (in the cell bodies but not in the fiber tracks); compared with AD patients expressing ApoE3
Comment In the MFG grey matter of AD patients with an ApoE4 genotype, there were increased levels of cholesterol, and the cholesterol esters C16:0, and C18:1 (range 2.6- to 3.4-fold).
Formal Description
Interaction-ID: 78371

gene/protein mutant

APOE (isoform E4)

increases_quantity of

drug/chemical compound

Cholesterol ester C18:1

in the MFG (middle frontal gyrus) grey matter of AD patients (in the cell bodies but not in the fiber tracks); compared with AD patients expressing ApoE3
Comment In the MFG grey matter, there were significant decreases of sphingomyelin C22:0 (12.5-fold), and C24:0 (6.2-fold), and significant increases of ceramide C18:0 (2.0-fold) and C24:1 (1.8-fold) in ApoE4 compared with ApoE3 AD brain.
Formal Description
Interaction-ID: 78372

gene/protein mutant

APOE (isoform E4)

decreases_quantity of

drug/chemical compound

SM C24:0

in the MFG grey matter in ApoE4 compared with ApoE3 AD brain; (6.2-fold decrease)
Comment In the MFG white matter, while there were no significant differences in sphingomeylin, there were significant differences in ceramide C22:0 (2.6-fold increase), C24:0 (1.2-fold decrease), and sulfatide (1.7-fold increase), in ApoE4 vs. ApoE3 brain.
Formal Description
Interaction-ID: 78373

gene/protein mutant

APOE (isoform E4)

decreases_quantity of

drug/chemical compound

Ceramide C24:0

in the MFG white matter in ApoE4 vs. ApoE3 brain; (1.2-fold decrease)
Comment In the MFG white matter, while there were no significant differences in sphingomeylin, there were significant differences in ceramide C22:0 (2.6-fold increase), C24:0 (1.2-fold decrease), and sulfatide (1.7-fold increase), in ApoE4 vs. ApoE3 brain.
Formal Description
Interaction-ID: 78374

gene/protein mutant

APOE (isoform E4)

increases_quantity of

drug/chemical compound

Sulfatide

in the MFG white matter in ApoE4 vs. ApoE3 brain; (1.7-fold increase)
Comment Ceramides C18:0, C24:1 and sulfatide were increased in the MFG (middle frontal gyrus) grey matter of ApoE4 AD patients (1.8- to 2.0-fold).
Formal Description
Interaction-ID: 78377

gene/protein mutant

APOE (isoform E4)

increases_quantity of

drug/chemical compound

Ceramide C24:1

in the MFG grey matter of ApoE4 AD patients
Comment Ceramides C18:0, C24:1 and sulfatide were increased in the MFG (middle frontal gyrus) grey matter of ApoE4 AD patients (1.8- to 2.0-fold).
Formal Description
Interaction-ID: 78378

gene/protein mutant

APOE (isoform E4)

increases_quantity of

drug/chemical compound

Sulfatide

in the MFG grey matter of ApoE4 AD patients