ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience1998
Increased synaptic sprouting in response to estrogen via an apolipoprotein E-dependent mechanism: implications for Alzheimer's disease.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
64 citing papers in PubMed, 1 synthesis or guideline pooled it, 240 citations in OpenAlex.
- Is Hormone Replacement Therapy a Risk Factor or a Therapeutic Option for Alzheimer's Disease?International journal of molecular sciences · 2023Pooled it
- Accelerated cell aging in female APOE-ε4 carriers: implications for hormone therapy use.PloS one · 2013Trial
- Evidence of APOE4-related brain vulnerabilities in verbal memory systems in midlife women.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Women's midlife: the front line of Alzheimer prevention.The Journal of clinical investigation · 2026Review
- Alzheimer's disease protective allele of Clusterin modulates neuronal excitability through lipid-droplet-mediated neuron-glia communication.Molecular neurodegeneration · 2025Article
- Apolipoprotein E in Alzheimer's Disease: Focus on Synaptic Function and Therapeutic Strategy.Molecular neurobiology · 2025Review
- Alzheimer's disease protective allele ofmedRxiv : the preprint server for health sciences · 2024Article
- Sex as a Determinant of Age-Related Changes in the Brain.International journal of molecular sciences · 2024Review
- The role of oestrogen therapy in reducing risk of Alzheimer's disease: systematic review.BJPsych open · 2023Review
- Role of estrogen in women's Alzheimer's disease risk as modified by APOE.Journal of neuroendocrinology · 2023Review
- The Effects of Modified Curcumin Preparations on Glial Morphology in Aging and Neuroinflammation.Neurochemical research · 2022Review
- The extracellular chaperone Clusterin enhances Tau aggregate seeding in a cellular model.Nature communications · 2021Article
- Precision hormone therapy: identification of positive responders.Climacteric : the journal of the International Menopause Society · 2021Review
- Disease progression modelling from preclinical Alzheimer's disease (AD) to AD dementia.Scientific reports · 2021Article
- Sex-Dependent Effects of the APOE ɛ4 Allele on Behavioral Traits and White Matter Structures in Young Adults.Cerebral cortex (New York, N.Y. : 1991) · 2021Article
- Women's brain aging: Effects of sex-hormone exposure, pregnancies, and genetic risk for Alzheimer's disease.Human brain mapping · 2020Article
- LMDS-1, a potential TrkB receptor agonist provides a safe and neurotrophic effect for early-phase Alzheimer's disease.Psychopharmacology · 2020Article
- Role of Ovarian Hormones in the Modulation of Sleep in Females Across the Adult Lifespan.Endocrinology · 2020Review
- Estrogen Signaling in Alzheimer's Disease: Molecular Insights and Therapeutic Targets for Alzheimer's Dementia.Molecular neurobiology · 2020Review
- The Role of Sex and Sex Hormones in Neurodegenerative Diseases.Endocrine reviews · 2020Review
4 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Estrogen replacement therapy appears to delay the onset of Alzheimer's disease (AD), but the mechanisms for this action are incompletely known. We show how the enhancement of synaptic sprouting by estradiol (E2) in response to an entorhinal cortex (EC) lesion model of AD may operate via an apolipoprotein E (apoE)-dependent mechanism. In wild-type (WT) mice, ovariectomy decreased commissural/associational sprouting to the inner molecular layer of the dentate gyrus, with synaptophysin (SYN) as a marker. E2 replacement returned SYN in the inner layer to levels of EC-lesioned, ovary-bearing controls and increased the area of compensatory synaptogenesis in the outer molecular layer. In EC-lesioned apoE-knock-out (KO) mice, however, E2 did not enhance sprouting. We also examined apoJ (clusterin) mRNA, which is implicated in AD by its presence in senile plaques, its transport of Abeta across the blood-brain barrier, and its induction by neurodegenerative lesioning. ApoJ mRNA levels were increased by E2 replacement in EC-lesioned WT mice but not in apoE-KO mice. These data suggest a mechanism for the protective effects of estrogens on AD and provide a link between two important risk factors in the etiology of AD, the apoE epsilon4 genotype and an estrogen-deficient state. This is also the first evidence that SYN, a presynaptic protein involved in neurotransmitter release, is regulated by E2 in the adult brain, and that apoE is necessary for the induction of apoJ mRNA by E2 in brain injury.
Indexed as
Identifiers
9547226PMC6792662W2109137609What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.