Resolving the relationship between ApolipoproteinE and depression

Slifer, Michael A.; Martin, Eden R.; Gilbert, John R.; Haines, Jonathan L.; Pericak‐Vance, Margaret A.

doi:10.1016/j.neulet.2009.03.007

Cited by 25 publications

(15 citation statements)

References 38 publications

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“…Verification of postmenopausal status was confirmed by plasma levels of follicle stimulating hormone (≥40 mIU/ml) and current estrogen usage was substantiated by pharmacy records. All study participants were cognitively intact with at least one or more of the following putative risk factors for AD: first-degree family history of AD 29, 30, presence of the apolipoprotein (APOE) ε4 allele, history of a major mood disorder (depression or bipolar disorder) 31–35, and/or history of hypothyroidism 36–39. However, only women with a history of hypothyroidism were included in the study only if the hypothyroidism was treated and medically stable.…”

Section: Methodsmentioning

confidence: 99%

Differences in Verbal Memory Performance in Postmenopausal Women Receiving Hormone Therapy: 17β-Estradiol Versus Conjugated Equine Estrogens

Wroolie

Kenna

Williams

et al. 2011

The American Journal of Geriatric Psychiatry

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Objective-Much controversy exists and many questions remain unanswered about the effects of hormone therapy (HT) on cognition in postmenopausal women. There is growing evidence suggesting that HT compounds containing conjugated equine estrogen (CEE) have negative effects on cognition whereas 17β-estradiol (17β-E) either has positive or neutral effects. The present study sought to further examine this issue in a sample of postmenopausal women with risk factors for Alzheimer's disease (AD).Design-Cross-sectional neuropsychological evaluation, as part of a larger longitudinal study. Setting-Academic research clinic.Participants-68 healthy postmenopausal women (aged 49-68) receiving either 17β-E or CEE for at least one year and at increased risk for Alzheimer's disease (AD).Measurements-Neuropsychological test battery of the cognitive domains of attention/working memory/processing speed, verbal memory, visual memory, and executive functioning.Results-Women receiving 17β-E showed significantly better verbal memory performance compared to women receiving CEE, regardless of age, IQ, years of education, risk factors for AD (including APOE-ε4 carriership), duration of endogenous and exogenous estrogen exposure, concurrent progesterone use, or natural or surgical menopause status.Conclusions-Verbal memory performance was better in menopausal women receiving 17β-E compared to CEE in a sample population of women with risk factors for AD. Genetic risk for AD as well as other confounds did not affect this finding. The results suggest that differential effect of the type of HT on verbal memory, with 17β-E being a preferential compound. Further evaluation of HT types, regimens and duration of use on cognitive performance in postmenopausal women in a controlled longitudinal design is warranted.

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Section: Methodsmentioning

confidence: 99%

Differences in Verbal Memory Performance in Postmenopausal Women Receiving Hormone Therapy: 17β-Estradiol Versus Conjugated Equine Estrogens

Wroolie

Kenna

Williams

et al. 2011

The American Journal of Geriatric Psychiatry

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“…PS1 and PS2 are components of the membrane-associated ␥-secretase protease complex that cleaves the amyloid precursor protein into non-toxic A␤-(1-40) and toxic A␤-(1-42) peptides (35,38). Intriguingly, a mutation that affects the splicing of the UBQLN mRNA has been associated with increased AD risk (39). Given the links between UBQLN and neurodegenerative disease, we explored its potential functional links to TDP-43.…”

Section: Ubqln Is a Tdp-43-interacting Protein-mentioning

confidence: 99%

Potentiation of Amyotrophic Lateral Sclerosis (ALS)-associated TDP-43 Aggregation by the Proteasome-targeting Factor, Ubiquilin 1

Kim¹,

Shi²,

Hanson³

et al. 2009

Journal of Biological Chemistry

108

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Amyotrophic lateral sclerosis (ALS)5 is a progressive, typically fatal, neurodegenerative disease that targets motor neurons (1). The cumulative lifetime risk for ALS is ϳ1 in 1000, which is comparable with the occurrence rate of multiple sclerosis (1). However, only about 3,000 cases of ALS are observed at any given time in the United States, because of the low fiveyear median survival rate (20%) for this disease. There are currently no effective treatments to halt the course of ALS.Approximately 10% of ALS cases, termed familial ALS (fALS), have a clear genetic link. Dominant mutations in the Cu,Zn-superoxide dismutase 1 (SOD1) are responsible for ϳ20% of fALS (2). Well over 100 different disease-associated mutations in SOD1 have been identified in humans (3). The mutations occur throughout the SOD1 open reading frame and do not alter the catalytic properties of the SOD1 enzyme per se (4). Instead, mutant SOD1 proteins are thought to acquire an abnormal fold that confers a toxic gain-of-function activity (4). Multiple cellular processes, including mitochondrial function, axon transport, and glutamate transporter function are adversely affected by toxic SOD1 mutants (5-10). Remarkably, mouse models of SOD1-induced ALS have shown that it is not a neuron-autonomous disease; expression of toxic SOD1 mutants in non-neuronal glial cells is sufficient to induce neuron pathology, whereas expression of toxic SOD1 mutants in motor neurons is insufficient for full expression of the disease phenotype (11,12). The SOD1 mouse model has been used to test candidate ALS therapeutics, including gene therapies directed toward silencing toxic SOD1 alleles in fALS (13)(14)(15).Sporadic ALS (sALS), representing 90 -95% of all ALS cases, occurs in the absence of a family history of disease, but follows a clinical course that is similar to SOD1 ALS. A hallmark of sALS is the presence of ubiquitin (Ub)-positive cytosolic aggregates in degenerating motor neurons (16). Recently, Neumann et al. (17) demonstrated that the 43-kDa human immunodeficiency virus transactivating region DNA-binding domain protein (TDP-43) is a major protein component of ubiquitin-positive aggregates in patients with sALS or ubiquitin-positive fronto-temporal lobular dementia. First identified as a binding factor of the long-terminal repeat region of the human immunodeficiency virus genome, TDP-43 is a nuclear RNA-binding protein that regulates splicing of the cystic fibrosis transmembrane conductance regulator mRNA (18 -20). Inactivation of TDP-43 through RNA interference caused enhanced transcription of cyclin-dependent kinase 6, hyperphosphorylation of the

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“…Apolipoprotein Ee4 (APOEe4) is a well-recognised risk factor for Alzheimer's disease (AD) but has also been implicated as a potential risk factor for neuropsychiatric disorders. Several studies have reported an association between APOE4 and depressive phenomenology (Slifer et al, 2009), but the pathophysiological substrate of this relationship is not yet clear. APOE is involved in the clearance of soluble amyloid b, and the e4 allele seems to be less efficient (Jiang et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Depression in mild dementia: associations with diagnosis, APOE genotype and clinical features

Fritze

Ehrt

Sønnesyn

et al. 2010

Int J Geriat Psychiatry

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Resolving the relationship between ApolipoproteinE and depression

Cited by 25 publications

References 38 publications

Differences in Verbal Memory Performance in Postmenopausal Women Receiving Hormone Therapy: 17β-Estradiol Versus Conjugated Equine Estrogens

Differences in Verbal Memory Performance in Postmenopausal Women Receiving Hormone Therapy: 17β-Estradiol Versus Conjugated Equine Estrogens

Potentiation of Amyotrophic Lateral Sclerosis (ALS)-associated TDP-43 Aggregation by the Proteasome-targeting Factor, Ubiquilin 1

Depression in mild dementia: associations with diagnosis, APOE genotype and clinical features

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