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Introduction: Clinical assessment of mood and anxiety change often relies on clinical assessment or self-reported scales. Using smartphone digital phenotyping data and resulting markers of behavior (e.g., sleep) to augment clinical symptom scores offers a scalable and potentially more valid method to understand changes in patients' state. This paper explores the potential of using a combination of active and passive sensors in the context of smartphone-based digital phenotyping to assess mood and anxiety changes in two distinct cohorts of patients to assess the preliminary reliability and validity of this digital phenotyping method., Methods: Participants from two different cohorts, each n = 76, one with diagnoses of depression/anxiety and the other schizophrenia, utilized mindLAMP to collect active data (e.g., surveys on mood/anxiety), along with passive data consisting of smartphone digital phenotyping data (geolocation, accelerometer, and screen state) for at least 1 month. Using anomaly detection algorithms, we assessed if statistical anomalies in the combination of active and passive data could predict changes in mood/anxiety scores as measured via smartphone surveys., Results: The anomaly detection model was reliably able to predict symptom change of 4 points or greater for depression as measured by the PHQ-9 and anxiety as measured for the GAD-8 for both patient populations, with an area under the ROC curve of 0.65 and 0.80 for each respectively. For both PHQ-9 and GAD-7, these AUCs were maintained when predicting significant symptom change at least 7 days in advance. Active data alone predicted around 52% and 75% of the symptom variability for the depression/anxiety and schizophrenia populations respectively., Conclusion: These results indicate the feasibility of anomaly detection for predicting symptom change in transdiagnostic cohorts. These results across different patient groups, different countries, and different sites (India and the US) suggest anomaly detection of smartphone digital phenotyping data may offer a reliable and valid approach to predicting symptom change. Future work should emphasize prospective application of these statistical methods., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Measurement-based peer supervision is one strategy to assure the quality of psychological treatments delivered by non-mental health specialist providers. In this formative study, we aimed to 1) describe the development and 2) examine the acceptability and feasibility of PEERS (Promoting Effective mental healthcare through peER Supervision)-a novel smartphone app that aims to facilitate registering and scheduling patients, collecting patient outcomes, rating therapy quality and assessing supervision quality-among frontline treatment providers delivering behavioral activation treatment for depression. The PEERS prototype was developed and tested in 2021, and version 1 was launched in 2022. To date, 215 treatment providers (98% female; ages 30-35) in Madhya Pradesh and Goa, India, have been trained to use PEERS and 65.58% have completed the supplemental, virtual PEERS course. Focus group discussions with 98 providers were examined according to four themes-training and education, app effectiveness, user experience and adherence and data privacy and safety. This yielded commonly endorsed facilitators (e.g., collaborative learning through group supervision, the convenience of consolidated patient data), barriers (e.g., difficulties with new technologies) and suggested changes (e.g., esthetic improvements, suicide risk assessment prompt). The PEERS app has the potential to scale measurement-based peer supervision to facilitate quality assurance of psychological treatments across contexts., Competing Interests: The authors have no conflicts of interest to disclose., (© The Author(s) 2024.)

Background: Receiving a diagnosis that leads to severe disability in childhood can cause a traumatic experience with long-lasting emotional stress for patients and family members. In recent decades, emerging digital technologies have transformed how patients or caregivers of persons with disabilities manage their health conditions. As a result, information (eg, on treatment and resources) has become widely available to patients and their families. Parents and other caregivers can use digital platforms such as websites or social media to derive social support, usually from other patients and caregivers who share their lived experiences, challenges, and successes on these platforms. However, gaps remain in our understanding of platforms that are most frequently used or preferred among parents and caregivers of children with disabilities. In particular, it is not clear what factors primarily drive or discourage engagement with these digital tools and what the main ethical considerations are in relation to these tools., Objective: We aimed to (1) identify prominent digital platforms used by parents or caregivers of children with disabilities; (2) explore the theoretical contexts and reasons for digital platform use, as well as the experiences made with using these platforms reported in the included studies; and (3) identify any privacy and ethical concerns emerging in the available literature in relation to the use of these platforms., Methods: We conducted a scoping review of 5 academic databases of English-language articles published within the last 10 years for diseases with childhood onset disability and self-help or parent/caregiver-led digital platforms., Results: We identified 17 papers in which digital platforms used by parents of affected children predominantly included social media elements but also search engines, health-related apps, and medical websites. Information retrieval and social support were the main reasons for their utilization. Nearly all studies were exploratory and applied either quantitative, qualitative, or mixed methods. The main ethical concerns for digital platform users included hampered access due to language barriers, privacy issues, and perceived suboptimal advice (eg, due to missing empathy of medical professionals). Older and non-college-educated individuals and ethnic minorities appeared less likely to access information online., Conclusions: This review showed that limited scientifically sound knowledge exists on digital platform use and needs in the context of disabling conditions in children, as the evidence consists mostly of exploratory studies. We could highlight that affected families seek information and support from digital platforms, as health care systems seem to be insufficient for satisfying knowledge and support needs through traditional channels., (©Oliver Gruebner, Afua van Haasteren, Anna Hug, Suzanne Elayan, Martin Sykora, Emiliano Albanese, John Naslund, Markus Wolf, Marta Fadda, Michael von Rhein. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 06.12.2022.)

Background: Physical, emotional, and social changes, including exposure to poverty, abuse, or violence, increases youth vulnerability to mental illness. These factors interfere with development, limit opportunities, and hamper achievement of a fulfilling life as adults. Addressing these issues can lead to improved outcomes at the population level and better cost-effectiveness for health services. Cash transfer programs have been a promising way to address social drivers for poor mental health. However, it is still unclear which pathways and mechanisms explain the association between socioeconomic support and lower mental illness among youth. Therefore, we will evaluate the effect of social drivers on youth mental health-related hospitalizations and suicide, test mechanisms and pathways of a countrywide socioeconomic intervention, and examine the timing of the intervention during the life course., Methods: We will combine individual-level data from youth national hospitalization, mental health disorders and attempted suicide, suicide registries and notifications of violence, with large-scale databases, including "The 100 Million Brazilian Cohort", over an 18-year period (2001-2018). Several approaches will be used for the retrospective quasi-experimental impact evaluations, such as Regression Discontinuity Designs, Propensity Score Matching and difference-in-differences, combined with multivariable regressions for cohort analyses. We will run multivariate regressions based on hierarchical analysis approach to evaluate the association between important social drivers (mental health care, demographic and economic aspects) on mental health-related hospitalizations and suicide among youth. Furthermore, we will perform microsimulations to generate projections regarding how mental health-related hospitalizations and suicide trends will be in the future based on the current state, and how BFP implementation scenarios will affect these trends., Discussion: The results of this project will be of vital importance to guide policies and programs to improve mental health and reduce mental health-related hospitalizations and suicide in youth. It will provide information to improve the effectiveness of these programs worldwide. If cash transfers can decrease mental health problems among youth and reduce suicide., Competing Interests: The authors have declared that no competing interests exist.

Aim: The present study aimed to investigate the cross-sectional association between self-reported use of electronic wearable devices (EWDs) and the levels of physical activity among a representative sample of adults with depression and anxiety in the United States. Methods: For this cross-sectional study, data were pooled from the Health Information National Trends Survey 2019. A sample of 1,139 adults with self-reported depression and anxiety (60.9% women; mean age of 52.5 years) was analyzed. The levels of physical activity and prevalence of EWD utilization were self-reported. The chi-square tests were used to compare individual characteristics through the use of EWDs. Multivariable logistic regression was employed to investigate the association between EWDs and physical activity levels while adjusting for sociodemographic and health-related factors. Results: From the 1,139 adults with self-reported depression and anxiety, 261 (weighted percentage 28.1%) endorsed using EWD in the last year. After adjusting for covariates, the use of EWDs was only significantly associated with a higher odds of reporting intention to lose weight (OR 2.12; 95% CI 1.04, 4.35; p = 0.04). We found no association between the use of EWDs and meeting the national weekly recommendation for physical activity or resistance/strength exercise training. Conclusion: About three in 10 adults suffering from depression and anxiety in the United States reported using EWDs in the last year. The current study findings indicate that among people living with mental illness, EWD use is associated with higher odds of weight loss intent suggesting that EWDs may serve as an opening for the clinical interactions around physical health through identifying patients primed for behavior change. Further large-scale studies using randomized trial designs are needed to examine the causal relationships between EWDs and the physical activity of people with mental health conditions., Competing Interests: JF is supported by a University of Manchester Presidential Fellowship (P123958) and a UK Research and Innovation Future Leaders Fellowship (MR/T021780/1) and has received honoraria/consultancy fees from Atheneum, ParachuteBH and Nirakara, independent of this work. JT is supported by an American Psychiatric Association Research Fellowship. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Onyeaka, Firth, Enemuo, Muoghalu, Naslund, Baiden and Torous.)

Background: Depression and anxiety impact up to 1 in 5 pregnant and postpartum women worldwide. Yet, as few as 20% of these women are treated with frontline interventions such as evidence-based psychological treatments. Major barriers to uptake are the limited number of specialized mental health treatment providers in most settings, and problems with accessing in-person care, such as childcare or transportation. Task sharing of treatment to non-specialist providers with delivery on telemedicine platforms could address such barriers. However, the equivalence of these strategies to specialist and in-person models remains unproven., Methods: This study protocol outlines the Scaling Up Maternal Mental healthcare by Increasing access to Treatment (SUMMIT) randomized trial. SUMMIT is a pragmatic, non-inferiority test of the comparable effectiveness of two types of providers (specialist vs. non-specialist) and delivery modes (telemedicine vs. in-person) of a brief, behavioral activation (BA) treatment for perinatal depressive and anxiety symptoms. Specialists (psychologists, psychiatrists, and social workers with ≥ 5 years of therapy experience) and non-specialists (nurses and midwives with no formal training in mental health care) were trained in the BA protocol, with the latter supervised by a BA expert during treatment delivery. Consenting pregnant and postpartum women with Edinburgh Postnatal Depression Scale (EPDS) score of ≥ 10 (N = 1368) will be randomized to one of four arms (telemedicine specialist, telemedicine non-specialist, in-person specialist, in-person non-specialist), stratified by pregnancy status (antenatal/postnatal) and study site. The primary outcome is participant-reported depressive symptoms (EPDS) at 3 months post-randomization. Secondary outcomes are maternal symptoms of anxiety and trauma symptoms, perceived social support, activation levels and quality of life at 3-, 6-, and 12-month post-randomization, and depressive symptoms at 6- and 12-month post-randomization. Primary analyses are per-protocol and intent-to-treat. The study has successfully continued despite the COVID-19 pandemic, with needed adaptations, including temporary suspension of the in-person arms and ongoing randomization to telemedicine arms., Discussion: The SUMMIT trial is expected to generate evidence on the non-inferiority of BA delivered by a non-specialist provider compared to specialist and telemedicine compared to in-person. If confirmed, results could pave the way to a dramatic increase in access to treatment for perinatal depression and anxiety., Trial Registration: ClinicalTrials.gov NCT04153864 . Registered on November 6, 2019.

Aims and Method: This systematic review examines the effectiveness and cost-effectiveness of behavioural health integration into primary healthcare in the management of depression and unhealthy alcohol use in low- and middle-income countries. Following PRISMA guidelines, this review included research that studied patients aged ≥18 years with unhealthy alcohol use and/or depression of any clinical severity. An exploration of the models of integration was used to characterise a typology of behavioural health integration specific for low- and middle-income countries., Results: Fifty-eight articles met inclusion criteria. Studies evidenced increased effectiveness of integrated care over treatment as usual for both conditions. The economic evaluations found increased direct health costs but cost-effective estimates. The included studies used six distinct behavioural health integration models., Clinical Implications: Behavioural health integration may yield improved health outcomes, although it may require additional resources. The proposed typology can assist decision-makers to advance the implementation of integrated models.

Background: Predicting and preventing relapse presents a crucial opportunity and first step to improve outcomes and reduce the care gap for persons living with schizophrenia. Using commercially available smartphones and smartwatches, technology now affords opportunities to capture real-time and longitudinal profiles of patients' symptoms, cognition, physiology and social patterns. This novel data makes it possible to explore relationships between behaviours, physiology and symptoms, which may yield personalised relapse signals., Aims: Smartphone Health Assessment for Relapse Prevention (SHARP), an international mental health research study supported by the Wellcome Trust, will inform the development of a scalable and sharable digital health solution to monitor personal risk of relapse. The resulting technology will be studied toward predicting and preventing relapse among individuals diagnosed with serious mental illness., Method: SHARP is a two-phase study with research sites in Boston, Massachusetts, and Bangalore and Bhopal, India. During phase 1, focus groups will be conducted at each study site to collect feedback on the design and features available on mindLAMP, a digital health platform. Individuals with serious mental illness will use mindLAMP for the duration of a year during phase 2., Results: The results of the research outlined in this protocol will guide the development of technology and digital tools to help address pervasive challenges in global mental health., Conclusions: The digital tools developed as a result of this study, and participants' experiences using them, may offer insight into opportunities to expand digital mental health resources and optimize their utilisation around the world.

The rapid spread of COVID-19 and the devastating consequences to economies and healthcare systems around the world has highlighted the exigent need for accessible mental health support. Increasing use of mobile devices in Lower Middle-Income Countries (LMIC) such as India offers novel opportunity to expand treatment options and reach underserved populations. Prior efforts have utilized technology to redistribute or supplement clinical care but measurable outcomes of this research are limited. In this paper, we explain the structural barriers that prevent access to care and build on prior research to demonstrate how technology can be utilized to offer treatment if it is aided by education and technical support., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: This study used thematic content analysis to examine submissions to a youth mental health website, www.itsoktotalk.in, in India., Setting: We considered submissions made to the It's OK to Talk web platform during the first year of its operation (April 2017-March 2018), focusing specifically on website users based in India., Participants: We analysed 37 submissions by 33 authors aged 19-31 years (mean age 22 years) from seven Indian cities (New Delhi, Lucknow, Bengaluru, Mumbai, Pune, Hyderabad and Haryana). Eligible submissions were English-language first-person accounts of self-identified mental health problems, submitted in any media format for online publication by authors aged 18 years or older and who were based in India. Eight study participants were additionally involved in a focus group who contributed to the coding process and preparation of the final manuscript., Results: Four themes were identified: (1) living through difficulties; (2) mental health in context; (3) managing one's mental health and (4) breaking stigma and sharing hope. Overall, the participants expressed significant feelings of distress and hopelessness as a result of their mental health problems; many described the context of their difficulties as resulting from personal histories or wider societal factors; a general lack of understanding about mental health; and widespread stigma and other negative attitudes. Most participants expressed a desire to overcome mental health prejudice and discrimination., Conclusions: Personal narratives offer a window into young people's self-identified priorities and challenges related to mental health problems and recovery. Such insights can inform antistigma initiatives and other public awareness activities around youth mental health., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Aims: People with serious mental illness are increasingly turning to popular social media, including Facebook, Twitter or YouTube, to share their illness experiences or seek advice from others with similar health conditions. This emerging form of unsolicited communication among self-forming online communities of patients and individuals with diverse health concerns is referred to as peer-to-peer support. We offer a perspective on how online peer-to-peer connections among people with serious mental illness could advance efforts to promote mental and physical wellbeing in this group., Methods: In this commentary, we take the perspective that when an individual with serious mental illness decides to connect with similar others online it represents a critical point in their illness experience. We propose a conceptual model to illustrate how online peer-to-peer connections may afford opportunities for individuals with serious mental illness to challenge stigma, increase consumer activation and access online interventions for mental and physical wellbeing., Results: People with serious mental illness report benefits from interacting with peers online from greater social connectedness, feelings of group belonging and by sharing personal stories and strategies for coping with day-to-day challenges of living with a mental illness. Within online communities, individuals with serious mental illness could challenge stigma through personal empowerment and providing hope. By learning from peers online, these individuals may gain insight about important health care decisions, which could promote mental health care seeking behaviours. These individuals could also access interventions for mental and physical wellbeing delivered through social media that could incorporate mutual support between peers, help promote treatment engagement and reach a wider demographic. Unforeseen risks may include exposure to misleading information, facing hostile or derogatory comments from others, or feeling more uncertain about one's health condition. However, given the evidence to date, the benefits of online peer-to-peer support appear to outweigh the potential risks., Conclusion: Future research must explore these opportunities to support and empower people with serious mental illness through online peer networks while carefully considering potential risks that may arise from online peer-to-peer interactions. Efforts will also need to address methodological challenges in the form of evaluating interventions delivered through social media and collecting objective mental and physical health outcome measures online. A key challenge will be to determine whether skills learned from peers in online networks translate into tangible and meaningful improvements in recovery, employment, or mental and physical wellbeing in the offline world.

Current efforts to reduce the increased risk of premature death from preventable cardiovascular disease among adults with serious mental illness (SMI) through lifestyle change have had limited success. Engaging informal support systems to promote healthy behaviors in everyday life may increase the effectiveness of health promotion interventions targeting this at-risk population. In-depth semistructured interviews were conducted with 10 fitness trainers serving adults with SMI in a health promotion program at community mental health centers to explore their perspectives on the potential of enlisting support from significant others for health behavior change. Trainers reported that the majority of participants had a relative or significant other who influenced their health behaviors, and they saw potential value in involving them in efforts to improve health outcomes by extending support into participants' daily lives. They did not feel qualified to work with families of individuals with mental illness, but they were willing to partner with providers who had experience in this area. Social workers who practice with families could play a critical role on health promotion teams addressing cardiovascular risk in adults with SMI by using their skills and experiences to engage families in supporting a relative through the process of health behavior change.

Objective: To determine whether changes in brain biometals in Alzheimer disease (AD) and in normal brain tissue are tandemly associated with amyloid beta-peptide (Abeta) burden and dementia severity., Methods: The authors measured zinc, copper, iron, manganese, and aluminum and Abeta levels in postmortem neocortical tissue from patients with AD (n = 10), normal age-matched control subjects (n = 14), patients with schizophrenia (n = 26), and patients with schizophrenia with amyloid (n = 8). Severity of cognitive impairment was assessed with the Clinical Dementia Rating Scale (CDR)., Results: There was a significant, more than twofold, increase of tissue zinc in the AD-affected cortex compared with the other groups. Zinc levels increased with tissue amyloid levels. Zinc levels were significantly elevated in the most severely demented cases (CDR 4 to 5) and in cases that had an amyloid burden greater than 8 plaques/mm(2). Levels of other metals did not differ between groups., Conclusions: Brain zinc accumulation is a prominent feature of advanced Alzheimer disease (AD) and is biochemically linked to brain amyloid beta-peptide accumulation and dementia severity in AD.

Investigating correlates of tobacco smoking provides the only currently available opportunity of examining effects of long-term exposure of nicotinic receptors on a specific nicotinic agonist in human. Alzheimer-type pathology (Abeta and abnormally phosphorylated tau assessed on the basis of AT8 immunoreactivity) together with vascular markers has been compared in age-matched groups of normal elderly smokers and non-smokers in the entorhinal cortex, an area of noted age-related pathology. The density of total Abeta and diffuse Abeta immunoreactivity, together with formic acid-extractable Abeta42 but not Abeta40, was reduced in smokers (n = 10-18) compared with non-smokers (n = 10-20) (P < 0.05). There was also a reduced percentage of cortical and leptomeningeal vessels with associated Abeta immunoreactivity in smokers (n = 13) compared with non-smokers (n = 14) (P < 0.005 and 0.05, respectively). There was a significant inverse correlation between formic acid-extractable Abeta42 and pack years (n = 34, r = -0.389, P = 0.025), with a similar trend for total Abeta immunoreactivity which did not reach statistical significance (n = 30, r = -0.323, P = 0.082). In contrast, there were no significant group differences for vascular markers (collagen IV, alpha-actin or glucose transporter 1), AT8 immunoreactivity or phosphate-buffered saline-soluble Abeta peptides, and no significant associations with gender for any of the measured parameters. These findings are consistent with previously reported reductions in histologically assessed amyloid plaques in aged human brain associated with tobacco use and dramatic lessening of Abeta deposits in APPsw mice after nicotine treatment. Development of nicotinic drugs to protect against beta-amyloidosis as one of the principal pathological hallmarks of brain ageing and Alzheimer's disease is indicated.

The mutation L271V in exon 8 of the presenilin-1 (PS-1) gene was detected in an Alzheimer's disease pedigree. Neuropathological examination of affected individuals identified variant, large, non-cored plaques without neuritic dystrophy, reminiscent of cotton wool plaques. Biochemical analysis of L271V mutation showed that it increased secretion of the 42-amino acid amyloid-beta peptide, suggesting a pathogenic mutation. Analysis of PS-1 transcripts from the brains of two mutation carriers revealed a 17-50% increase in PS-1 transcripts with deletion of exon 8 (PS-1deltaexon8) compared with unrelated Alzheimer's disease brains. Exon trapping analysis confirmed that L271V mutation enhanced the deletion of exon 8. Western blots of brain lysates indicated that PS-1deltaexon8 was overexpressed in an affected individual. Biochemical analysis of PS-1deltaexon8 in COS and BD8 cells indicate the splice isoform is not intrinsically active but interacts with wild-type PS-1 to generate amyloid-beta. Western blots of cell lysates immunoprecipitated with anti-Tau or anti-GSK-3beta antibodies indicated that PS-1deltaexon8, unlike wild-type PS-1, does not interact directly with Tau or GSK-3beta, potential modifiers of neuritic dystrophy. We postulate that variant plaques observed in this family are due in part to the effects of PS-1deltaexon8 and that interaction between PS-1 and various protein complexes are necessary for neuritic plaque formation.

Alzheimer's disease is characterized by accumulation in the brain of a family of insoluble amyloid peptides (Abeta peptides), which are produced as a result of the normal processing of beta-amyloid precursor protein (beta-APP). Russo et al. claim that a truncated Abeta peptide that lacks the first ten amino acids accumulates in the brains of patients carrying a mutant form of pre-senilin 1 (PS1), a protein that is involved in cleavage of beta-APP. However, we have found that this same species is also overrepresented in Alzheimer's patients with mutations in beta-APP itself. Our findings do not support the conclusion of Russo et al. that pathogenic PS1 mutations may control cleavage of beta-APP by beta-secretase.

Background: Prior studies have shown that cyclooxygenase 2 (COX-2), an enzyme involved in inflammatory mechanisms and neuronal activities, is up-regulated in the brain with Alzheimer disease (AD) and may represent a therapeutic target for anti-inflammatory treatments., Objective: To explore COX-2 expression in the brain as a function of clinical progression of early AD., Design and Main Outcome Measures: Using semiquantitative immunocytochemistry, we analyzed COX-2 protein content in the hippocampal formation in 54 postmortem brain specimens from patients with normal or impaired cognitive status., Setting and Patients: Postmortem study of nursing home residents., Results: The immunointensity of COX-2 signal in the CA3 and CA2 but not CA1 subdivisions of the pyramidal layers of the hippocampal formation of the AD brain increased as the disease progressed from questionable to mild clinical dementia as assessed by Clinical Dementia Rating. COX-2 signal was increased in all 3 regions examined among cases characterized by severe dementia., Conclusion: Neuronal COX-2 content in subsets of hippocampal pyramidal neurons may be an indicator of progression of dementia in early AD.

Alzheimer's disease (AD) is characterized by the deposition of senile plaques (SPs) and neurofibrillary tangles (NFTs) in vulnerable brain regions. SPs are composed of aggregated beta-amyloid (Abeta) 40/42(43) peptides. Evidence implicates a central role for Abeta in the pathophysiology of AD. Mutations in betaAPP and presenilin 1 (PS1) lead to elevated secretion of Abeta, especially the more amyloidogenic Abeta42. Immunohistochemical studies have also emphasized the importance of Abeta42 in initiating plaque pathology. Cell biological studies have demonstrated that Abeta is generated intracellularly. Recently, endogenous Abeta42 staining was demonstrated within cultured neurons by confocal immunofluorescence microscopy and within neurons of PS1 mutant transgenic mice. A central question about the role of Abeta in disease concerns whether extracellular Abeta deposition or intracellular Abeta accumulation initiates the disease process. Here we report that human neurons in AD-vulnerable brain regions specifically accumulate gamma-cleaved Abeta42 and suggest that this intraneuronal Abeta42 immunoreactivity appears to precede both NFT and Abeta plaque deposition. This study suggests that intracellular Abeta42 accumulation is an early event in neuronal dysfunction and that preventing intraneuronal Abeta42 aggregation may be an important therapeutic direction for the treatment of AD.

Alzheimer's disease (AD) is characterized by the accumulation of cerebral plaques composed of 40- and 42-amino acid beta-amyloid (Abeta) peptides, and autosomal dominant forms of AD appear to cause disease by promoting brain Abeta accumulation. Recent studies indicate that postmenopausal estrogen replacement therapy may prevent or delay the onset of AD. Here we present evidence that physiological levels of 17beta-estradiol reduce the generation of Abeta by neuroblastoma cells and by primary cultures of rat, mouse and human embryonic cerebrocortical neurons. These results suggest a mechanism by which estrogen replacement therapy can delay or prevent AD.