General Information:

Id: 7,522
Diseases: Alzheimer disease - [OMIM]
Metabolic
Mammalia
review
Reference: Raber J(2008) AR, apoE, and cognitive function Horm Behav 53: 706-715 [PMID: 18395206]

Interaction Information:

Comment At 6 months of age, apoE4 female showed impairments in hippocampus-dependent spatial learning and memory in the water maze. These impairments were observed in mice that express apoE4 in neurons or astrocytes and are therefore independent of the cellular source of apoE. They require apoE4 and are not seen in Apoe-/- female mice, consistent with a pathogenic gain of function of apoE4.
Formal Description
Interaction-ID: 74174

gene/protein mutant

APOE (isoform E4)

decreases_activity of

process

spartial memory

in APOA4 female mice
Comment At 6 months of age, apoE4 female showed impairments in hippocampus-dependent spatial learning and memory in the water maze. These impairments were observed in mice that express apoE4 in neurons or astrocytes and are therefore independent of the cellular source of apoE. They require apoE4 and are not seen in Apoe-/- female mice, consistent with a pathogenic gain of function of apoE4.
Formal Description
Interaction-ID: 74176

gene/protein mutant

APOE (isoform E4)

decreases_activity of

process

memory

in APOA4 female mice
Comment Effects of apoE4 on AR function might contribute to these cognitive impairments. Treatment of 6-month apoE4 female mice with testosterone or dihydrotestosterone antagonized these impairments
Formal Description
Interaction-ID: 74177

drug/chemical compound

Testosterone

increases_activity of

process

spartial memory

in APOA4 female mice
Drugbank entries Show/Hide entries for Testosterone
Comment Effects of apoE4 on AR function might contribute to these cognitive impairments. Treatment of 6-month apoE4 female mice with testosterone or dihydrotestosterone antagonized these impairments
Formal Description
Interaction-ID: 74181

drug/chemical compound

Dihydrotestosterone

increases_activity of

process

spartial memory

in APOA4 female mice
Drugbank entries Show/Hide entries for Dihydrotestosterone
Comment Compared to age-matched wild-type and Apoe−/− mice, expression of apoE4, but not apoE3, reduces cytosolic AR binding to androgens in the neocortex of female and male mice
Formal Description
Interaction-ID: 74183

drug/chemical compound

Testosterone

interacts (colocalizes) with

gene/protein

AR

Drugbank entries Show/Hide entries for Testosterone or AR
Comment Compared to age-matched wild-type and Apoe-/- mice, expression of apoE4, but not apoE3, reduces cytosolic AR binding to androgens in the neocortex of female and male mice
Formal Description
Interaction-ID: 74185

gene/protein mutant

APOE (isoform E4)

decreases_activity of

gene/protein

AR

Drugbank entries Show/Hide entries for AR
Comment The mouse apoE colocalizes with AR in astrocytes.
Formal Description
Interaction-ID: 74186

gene/protein

APOE

interacts (colocalizes) with

gene/protein

AR

in astrocytes
Drugbank entries Show/Hide entries for APOE or AR
Comment In cortical extracts, more AR was pulled down from extracts of NSE-apoE4 than NSE-apoE3 mice. GST-apoE proteins pull down ARs from cortical extracts of Apoe−/− mice and that GST-apoE4 might pull down more ARs than GST-apoE3 or GST-apoE2.
Formal Description
Interaction-ID: 74188

gene/protein mutant

APOE (isoform E2)

interacts (colocalizes) with

gene/protein

AR

in cortical extracts; in Apo-/- mice
Drugbank entries Show/Hide entries for AR
Comment In cortical extracts, more AR was pulled down from extracts of NSE-apoE4 than NSE-apoE3 mice. GST-apoE proteins pull down ARs from cortical extracts of Apoe−/− mice and that GST-apoE4 might pull down more ARs than GST-apoE3 or GST-apoE2.
Formal Description
Interaction-ID: 74189

gene/protein mutant

APOE (isoform E3)

interacts (colocalizes) with

gene/protein

AR

in cortical extracts; in Apo-/- mice
Drugbank entries Show/Hide entries for AR
Comment In cortical extracts, more AR was pulled down from extracts of NSE-apoE4 than NSE-apoE3 mice. GST-apoE proteins pull down ARs from cortical extracts of Apoe−/− mice and that GST-apoE4 might pull down more ARs than GST-apoE3 or GST-apoE2.
Formal Description
Interaction-ID: 74190

gene/protein mutant

APOE (isoform E4)

interacts (colocalizes) with

gene/protein

AR

in cortical extracts; in Apo-/- mice
Drugbank entries Show/Hide entries for AR
Comment In the vertical limb of the diagonal band of Broca, a major cholinergic nucleus in the basal forebrain affected in AD, the presence of AD pathology or an ε4 allele negatively correlates with the percentage of AR-positive neurons in women, but not in men.
Formal Description
Interaction-ID: 74192

decreases_quantity of

tissue/cell line

AR-positive neurons

in female
Comment In the vertical limb of the diagonal band of Broca, a major cholinergic nucleus in the basal forebrain affected in AD, the presence of AD pathology or an ε4 allele negatively correlates with the percentage of AR-positive neurons in women, but not in men.
Formal Description
Interaction-ID: 74194

NOT affects_quantity of

tissue/cell line

AR-positive neurons

in male
Comment In the vertical limb of the diagonal band of Broca, a major cholinergic nucleus in the basal forebrain affected in AD, the presence of AD pathology or an ε4 allele negatively correlates with the percentage of AR-positive neurons in women, but not in men.
Formal Description
Interaction-ID: 74196

gene/protein mutant

APOE (isoform E4)

decreases_quantity of

tissue/cell line

AR-positive neurons

in female
Comment In the vertical limb of the diagonal band of Broca, a major cholinergic nucleus in the basal forebrain affected in AD, the presence of AD pathology or an ε4 allele negatively correlates with the percentage of AR-positive neurons in women, but not in men.
Formal Description
Interaction-ID: 74197

gene/protein mutant

APOE (isoform E4)

NOT affects_quantity of

tissue/cell line

AR-positive neurons

in male
Comment Altered AR function resulting from a polymorphism in the glutamine (CAG) repeats in exon 1 of the AR gene might increase AD risk; 20 or fewer CAG repeats are associated with increased AD risk in men, but not women, particularly in those lacking the E4 allele
Formal Description
Interaction-ID: 74198

gene/protein mutant

AR-mutant (CAGs repeats)

increases_activity of

in male ; in male
Comment As polymorphisms in the CAG repeats correlate with altered AR transcription and translation (the more CAGs the less active AR), these data indicate that enhanced AR function might be beneficial for E4, but not for non-E4 carriers.
Formal Description
Interaction-ID: 74199

gene/protein mutant

AR-mutant (CAGs repeats)

decreases_activity of

gene/protein

AR

Drugbank entries Show/Hide entries for AR
Comment Altered AR function resulting from a polymorphism in the glutamine (CAG) repeats in exon 1 of the AR gene might increase AD risk; 20 or fewer CAG repeats are associated with increased AD risk in men, but not women, particularly in those lacking the E4 allele
Formal Description
Interaction-ID: 74201

gene/protein mutant

AR-mutant (CAGs repeats)

NOT affects_activity of

in female with APOE4 allele