Memory loss in Alzheimer's disease: are the alterations in the UPR network involved in the cognitive impairment?

Artículo de publicación ISIThis work was funded by the Alzheimer Disease Association, Millennium Institute no. P09-015-F, FONDECYT no. 1100176, ACT1109; CONICYT grant USA2013-0003, ECOS-CONICYTC13S02 and FONDEF D11I1007 (Claudio Hetz), Doctoral Fellow supported by CONICYT (Gabriela Martínez) and FONDECYT grant no. 3140466 (Claudia Duran-Aniotz)

Latin American women in dementia research: outstanding contributions, barriers, and opportunities from Argentinian, Chilean, and Colombian colleagues

Women’s contributions to science have been consistently underrepresented throughout history. Despite many efforts and some progresses being made to reduce gender inequity in science, pursuing an academic career across disciplines, including Alzheimer’s disease (AD) and other dementias, remains challenging for women. Idiosyncratic difficulties of Latin American countries likely accentuate the gender gap. In this Perspective, we celebrate outstanding contributions from Argentinian, Chilean, and Colombian colleagues in dementia research and discuss barriers and opportunities identified by them. We aim to acknowledge Latin American women’s work and bring visibility to the challenges they face throughout their careers in order to inform potential solutions. Also, we highlight the need to perform a systematic assessment of the gender gap in the Latin American dementia community of researchers

Endoplasmic reticulum proteostasis impairment in aging

Summary Perturbed neuronal proteostasis is a salient feature shared by both aging and protein misfolding disorders. The proteostasis network controls the health of the proteome by integrating pathways involved in protein synthesis, folding, trafficking, secretion, and their degradation. A reduction in the buffering capacity of the proteostasis network during aging may increase the risk to undergo neurodegeneration by enhancing the accumulation of misfolded proteins. As almost one‐third of the proteome is synthetized at the endoplasmic reticulum (ER), maintenance of its proper function is fundamental to sustain neuronal function. In fact, ER stress is a common feature of most neurodegenerative diseases. The unfolded protein response (UPR) operates as central player to maintain ER homeostasis or the induction of cell death of chronically damaged cells. Here, we discuss recent evidence placing ER stress as a driver of brain aging, and the emerging impact of neuronal UPR in controlling global proteostasis at the whole organismal level. Finally, we discuss possible therapeutic interventions to improve proteostasis and prevent pathological brain aging

Systematic Review: microRNAs as Potential Biomarkers in Mild Cognitive Impairment Diagnosis

The rate of progression from Mild Cognitive Impairment (MCI) to Alzheimer's disease (AD) is estimated at >10% per year, reaching up to 80–90% after 6 years. MCI is considered an indicator of early-stage AD. In this context, the diagnostic screening of MCI is crucial for detecting individuals at high risk of AD before they progress and manifest further severe symptoms. Typically, MCI has been determined using neuropsychological assessment tools such as the Montreal Cognitive Assessment (MoCA) or Mini-Mental Status Examination (MMSE). Unfortunately, other diagnostic methods are not available or are unable to identify MCI in its early stages. Therefore, identifying new biomarkers for MCI diagnosis and prognosis is a significant challenge. In this framework, miRNAs in serum, plasma, and other body fluids have emerged as a promising source of biomarkers for MCI and AD-related cognitive impairments. Interestingly, miRNAs can regulate several signaling pathways via multiple and diverse targets in response to pathophysiological stimuli. This systematic review aims to describe the current state of the art regarding AD-related target genes modulated by differentially expressed miRNAs in peripheral fluids samples in MCI subjects to identify potential miRNA biomarkers in the early stages of AD. We found 30 articles that described five miRNA expression profiles from peripheral fluid in MCI subjects, showing possible candidates for miRNA biomarkers that may be followed up as fluid biomarkers or therapeutic targets of early-stage AD. However, additional research is needed to validate these miRNAs and characterize the precise neuropathological mechanisms.Fil: Ogonowski, Natalia Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; Argentina. Universidad Adolfo Ibañez; ChileFil: Salcidua, Stefanny. Universidad Adolfo Ibañez; ChileFil: Leon, Tomas. Universidad de Chile; Chile. Trinity College; IrlandaFil: Chamorro Veloso, Nayaret. Neurognos Spa; ChileFil: Valls, Cristian. Neurognos Spa; ChileFil: Avalos, Constanza. Universidad Adolfo Ibañez; ChileFil: Bisquertt, Alejandro. Neurognos Spa; ChileFil: Rentería, Miguel E.. Berghofer Medical Research Institute; AustraliaFil: Orellana, Paulina. Universidad Adolfo Ibañez; ChileFil: Duran Aniotz, Claudia. Universidad Adolfo Ibañez; Chil

The impact of SARS-CoV-2 in dementia across Latin America : A call for an urgent regional plan and coordinated response

The SARS-CoV-2 global pandemic will disproportionately impact countries with weak economies and vulnerable populations including people with dementia. Latin American and Caribbean countries (LACs) are burdened with unstable economic development, fragile health systems, massive economic disparities, and a high prevalence of dementia. Here, we underscore the selective impact of SARS-CoV-2 on dementia among LACs, the specific strain on health systems devoted to dementia, and the subsequent effect of increasing inequalities among those with dementia in the region. Implementation of best practices for mitigation and containment faces particularly steep challenges in LACs. Based upon our consideration of these issues, we urgently call for a coordinated action plan, including the development of inexpensive mass testing and multilevel regional coordination for dementia care and related actions. Brain health diplomacy should lead to a shared and escalated response across the region, coordinating leadership, and triangulation between governments and international multilateral networks

Advancements in dementia research, diagnostics and care in Latin America : highlights from the 2023 Alzheimer's association international conference satellite symposium in Mexico City

While Latin America (LatAm) is facing an increasing burden of dementia due to the rapid aging of the population, it remains underrepresented in dementia research, diagnostics and care. In 2023, the Alzheimer’s Association hosted its eighth Satellite Symposium in Mexico, highlighting emerging dementia research, priorities, and challenges within LatAm. A wide range of topics were covered, including epidemiology, social determinants, dementia national plans, risk reduction, genetics, biomarkers, biobanks, and advancements in treatments. Large initiatives in the region including intra-country support showcased their efforts in fostering national and international collaborations; genetic studies unveiled the unique genetic admixture in LatAm; emerging clinical trials discussed ongoing culturally specific interventions; and the urgent need to harmonize practices and studies, improve diagnosis and care and implement affordable biomarkers in the region was highlighted