Breast cancer therapies reduce risk of Alzheimer’s disease and promote estrogenic pathways and action in brain

Branigan, Gregory L.; Torrandell-Haro, Georgina; Chen, Shuhua; Shang, Yuan; Perez-Miller, Samantha; Mao, Zisu; Padilla-Rodriguez, Marco; Cortes-Flores, Helena; Vitali, Francesca; Brinton, Roberta Diaz

doi:10.1016/j.isci.2023.108316

Cited by 4 publications

(3 citation statements)

References 105 publications

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“…The physiological functions of COX 4 may experience a decline in elderly populations, plausibly attributable to the buildup of oxidative harm to mitochondrial DNA . However, females who have been diagnosed with AD may encounter a more significant accumulation of oxidative stress caused by mitochondrial dysfunction in contrast to those who do not have the disease (Branigan et al, 2023). Moreover, the disruption was correlated with a reduction in the expression of neuronal ERβ (Upadhayay et al, 2023).…”

Section: The Role Of Erβ In the Pathogenesis Of Admentioning

confidence: 98%

“…Several sources of evidence suggest that the targeted activation of ERβ may hold promise for enhancing cognitive function (Koire et al, 2022). Studies showed the positive impact of DPN on neuronal survival in the rat hippocampus (Branigan et al, 2023). This was achieved through the upregulation of the antiapoptotic protein Bcl-2 (Bortz et al, 2022).…”

Section: Targeting Ersmentioning

confidence: 99%

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Estrogen signalling and Alzheimer's disease: Decoding molecular mechanisms for therapeutic breakthrough

Rishabh,

Rohilla,

Bansal

et al. 2024

Eur J of Neuroscience

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In females, Alzheimer's disease (AD) incidences increases as compared to males due to estrogen deficiency after menopause. Estrogen therapy is the mainstay therapy for menopause and associated complications. Estrogen, a hormone with multifaceted physiological functions, has been implicated in AD pathophysiology. Estrogen plays a crucial role in amyloid precursor protein (APP) processing and overall neuronal health by regulating various factors such as brain‐derived neurotrophic factor (BDNF), intracellular calcium signalling, death domain‐associated protein (Daxx) translocation, glutamatergic excitotoxicity, Voltage‐Dependent Anion Channel, Insulin‐Like Growth Factor 1 Receptor, estrogen‐metabolising enzymes and apolipoprotein E (ApoE) protein polymorphisms. All these factors impact the physiology of postmenopausal women. Estrogen replacement therapies play an important treatment strategy to prevent AD after menopause. However, use of these therapies may lead to increased risks of breast cancer, venous thromboembolism and cardiovascular disease. Various therapeutic approaches have been used to mitigate the effects of estrogen on AD. These include hormone replacement therapy, Selective Estrogen Receptor Modulators (SERMs), Estrogen Receptor Beta (ERβ)‐Selective Agonists, Transdermal Estrogen Delivery, Localised Estrogen Delivery, Combination Therapies, Estrogen Metabolism Modulation and Alternative Estrogenic Compounds like genistein from soy, a notable phytoestrogen from plant sources. However, mechanism via which these approaches modulate AD in postmenopausal women has not been explained earlier thoroughly. Present review will enlighten all the molecular mechanisms of estrogen and estrogen replacement therapies in AD. Along‐with this, the association between estrogen, estrogen‐metabolising enzymes and ApoE protein polymorphisms will also be discussed in postmenopausal AD.

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Section: The Role Of Erβ In the Pathogenesis Of Admentioning

confidence: 98%

Section: Targeting Ersmentioning

confidence: 99%

Estrogen signalling and Alzheimer's disease: Decoding molecular mechanisms for therapeutic breakthrough

Rishabh,

Rohilla,

Bansal

et al. 2024

Eur J of Neuroscience

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“… 16 , 17 The existing research on the association of hormone therapy on ADRD risk is sparse and shows inconsistent results. 18 Some studies, including clinical trials and observational studies, suggest that HMT may lower the risk of cognitive conditions, such as mild cognitive impairment, 19 ADRD, 20 , 21 , 22 , 23 and neurodegenerative disease. 24 Other studies suggest that HMT could be associated with an increased risk of ADRD 25 , 26 , 27 , 28 , 29 or found no evidence to support the association.…”

Section: Introductionmentioning

confidence: 99%

Alzheimer Disease and Related Dementia Following Hormone-Modulating Therapy in Patients With Breast Cancer

Cai,

Strickland,

Knudsen

et al. 2024

JAMA Netw Open

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ImportanceHormone-modulating therapy (HMT) is a widely accepted treatment for hormone receptor–positive breast cancer, although its cognitive effects, including a potential link to Alzheimer disease and related dementias (ADRD), remain understudied.ObjectiveTo investigate the association between HMT for breast cancer treatment and risk of developing ADRD in women aged 65 years or older.Design, Setting, and ParticipantsThis cohort study used a comprehensive dataset from the Surveillance, Epidemiology, and End Results (SEER)–Medicare linked database to identify patients who did and did not receive HMT treatment within 3 years after the initial diagnosis of breast cancer and assessed their risk of developing ADRD in later life. Individuals with a preexisting diagnosis of ADRD or receiving HMT before the diagnosis of breast cancer were excluded. This study was performed from June 2022 through January 2024.ExposureReceipt of HMT.Main Outcomes and MeasuresRisk of ADRD associated with HMT; associations of risk with age, self-identified race, and HMT type. Risk was measured using hazard ratios (HRs) with 95% CIs and adjusted for potential confounders such as demographic, sociocultural, and clinical variables.ResultsAmong 18 808 women aged 65 years and older diagnosed with breast cancer between 2007 and 2009 (1266 Black [6.7%], 16 526 White [87.9%], 1016 other [5.4%]), 12 356 (65.7%) received HMT within 3 years after diagnosis, while 6452 (34.3%) did not. The most common age group in both samples was the 75 to 79 years age group (HMT, 2721 women [22.0%]; no HMT, 1469 women [22.8%]), and the majority of women in both groups self-identified as White (HMT, 10 904 women [88.3%]; no HMT, 5622 women [87.1%]). During an average of 12 years of follow-up, 2926 (23.7%) of HMT users and 1802 (27.9%) of non-HMT users developed ADRD. HMT was associated with a 7% lower relative risk of ADRD overall (HR, 0.93; 95% CI, 0.88-0.98; P = .005). The association decreased with age and varied by race. The reduction in ADRD risk associated with HMT was greatest for women aged 65 to 74 years who self-identified as Black (HR, 0.76; 95% CI, 0.62-0.92). This association decreased among women aged 75 years or older (HR, 0.81; 95% CI, 0.67-0.98). Women aged 65 to 74 years who self-identified as White had an 11% relative risk reduction (HR, 0.89; 95% CI, 0.81-0.97), but the association disappeared for women aged 75 years or older (HR, 0.96; 95% CI, 0.90-1.02). Other races showed no significant association between HMT and ADRD. Age- and race-based associations also varied by HMT type.Conclusions and RelevanceIn this retrospective cohort study, hormone therapy was associated with protection against ADRD in women aged 65 years or older with newly diagnosed breast cancer; the decrease in risk was relatively greater for Black women and women under age 75 years, while the protective effect of HMT diminished with age and varied by race in women. When deciding to use HMT for breast cancer in women aged 65 years or more, clinicians should consider age, self-identified race, and HMT type in treatment decisions.

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Letrozole delays acquisition of water maze task in female BALB/c mice: Possible involvement of anxiety

Mamczarz,

Lane,

Merchenthaler

2024

Hormones and Behavior

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Breast cancer therapies reduce risk of Alzheimer’s disease and promote estrogenic pathways and action in brain

Cited by 4 publications

References 105 publications

Estrogen signalling and Alzheimer's disease: Decoding molecular mechanisms for therapeutic breakthrough

Estrogen signalling and Alzheimer's disease: Decoding molecular mechanisms for therapeutic breakthrough

Alzheimer Disease and Related Dementia Following Hormone-Modulating Therapy in Patients With Breast Cancer

Letrozole delays acquisition of water maze task in female BALB/c mice: Possible involvement of anxiety

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