Revised criteria for diagnosis and staging of Alzheimer's disease: Alzheimer's Association Workgroup.

The National Institute on Aging and the Alzheimer's Association convened three separate work groups in 2011 and single work groups in 2012 and 2018 to create recommendations for the diagnosis and characterization of Alzheimer's disease (AD). The present document updates the 2018 research framework in response to several recent developments. Defining diseases biologically, rather than based on syndromic presentation, has long been standard in many areas of medicine (e.g., oncology), and is becoming a unifying concept common to all neurodegenerative diseases, not just AD. The present document is consistent with this principle. Our intent is to present objective criteria for diagnosis and staging AD, incorporating recent advances in biomarkers, to serve as a bridge between research and clinical care. These criteria are not intended to provide step-by-step clinical practice guidelines for clinical workflow or specific treatment protocols, but rather serve as general principles to inform diagnosis and staging of AD that reflect current science. HIGHLIGHTS: We define Alzheimer's disease (AD) to be a biological process that begins with the appearance of AD neuropathologic change (ADNPC) while people are asymptomatic. Progression of the neuropathologic burden leads to the later appearance and progression of clinical symptoms. Early-changing Core 1 biomarkers (amyloid positron emission tomography [PET], approved cerebrospinal fluid biomarkers, and accurate plasma biomarkers [especially phosphorylated tau 217]) map onto either the amyloid beta or AD tauopathy pathway; however, these reflect the presence of ADNPC more generally (i.e., both neuritic plaques and tangles). An abnormal Core 1 biomarker result is sufficient to establish a diagnosis of AD and to inform clinical decision making throughout the disease continuum. Later-changing Core 2 biomarkers (biofluid and tau PET) can provide prognostic information, and when abnormal, will increase confidence that AD is contributing to symptoms. An integrated biological and clinical staging scheme is described that accommodates the fact that common copathologies, cognitive reserve, and resistance may modify relationships between clinical and biological AD stages.

Novel avenues of tau research.

INTRODUCTION: The pace of innovation has accelerated in virtually every area of tau research in just the past few years. METHODS: In February 2022, leading international tau experts convened to share selected highlights of this work during Tau 2022, the second international tau conference co-organized and co-sponsored by the Alzheimer's Association, CurePSP, and the Rainwater Charitable Foundation. RESULTS: Representing academia, industry, and the philanthropic sector, presenters joined more than 1700 registered attendees from 59 countries, spanning six continents, to share recent advances and exciting new directions in tau research. DISCUSSION: The virtual meeting provided an opportunity to foster cross-sector collaboration and partnerships as well as a forum for updating colleagues on research-advancing tools and programs that are steadily moving the field forward.

Advancements in dementia research, diagnostics, and care in Latin America: Highlights from the 2023 Alzheimer's Association International conference satellite symposium in Mexico City.

INTRODUCTION: 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. METHODS: In 2023, the Alzheimer's Association hosted its eighth satellite symposium in Mexico, highlighting emerging dementia research, priorities, and challenges within LatAm. RESULTS: Significant initiatives in the region, including intracountry support, showcased their efforts in fostering national and international collaborations; genetic studies unveiled the unique genetic admixture in LatAm; researchers conducting emerging clinical trials discussed ongoing culturally specific interventions; and the urgent need to harmonize practices and studies, improve diagnosis and care, and use affordable biomarkers in the region was highlighted. DISCUSSION: The myriad of topics discussed at the 2023 AAIC satellite symposium highlighted the growing research efforts in LatAm, providing valuable insights into dementia biology, genetics, epidemiology, treatment, and care.

The 2022 symposium on dementia and brain aging in low- and middle-income countries: Highlights on research, diagnosis, care, and impact.

Two of every three persons living with dementia reside in low- and middle-income countries (LMICs). The projected increase in global dementia rates is expected to affect LMICs disproportionately. However, the majority of global dementia care costs occur in high-income countries (HICs), with dementia research predominantly focusing on HICs. This imbalance necessitates LMIC-focused research to ensure that characterization of dementia accurately reflects the involvement and specificities of diverse populations. Development of effective preventive, diagnostic, and therapeutic approaches for dementia in LMICs requires targeted, personalized, and harmonized efforts. Our article represents timely discussions at the 2022 Symposium on Dementia and Brain Aging in LMICs that identified the foremost opportunities to advance dementia research, differential diagnosis, use of neuropsychometric tools, awareness, and treatment options. We highlight key topics discussed at the meeting and provide future recommendations to foster a more equitable landscape for dementia prevention, diagnosis, care, policy, and management in LMICs. HIGHLIGHTS: Two-thirds of persons with dementia live in LMICs, yet research and costs are skewed toward HICs. LMICs expect dementia prevalence to more than double, accompanied by socioeconomic disparities. The 2022 Symposium on Dementia in LMICs addressed advances in research, diagnosis, prevention, and policy. The Nairobi Declaration urges global action to enhance dementia outcomes in LMICs.

Harmonizing tau positron emission tomography in Alzheimer's disease: The CenTauR scale and the joint propagation model.

INTRODUCTION: Tau-positron emission tomography (PET) outcome data of patients with Alzheimer's disease (AD) cannot currently be meaningfully compared or combined when different tracers are used due to differences in tracer properties, instrumentation, and methods of analysis. METHODS: Using head-to-head data from five cohorts with tau PET radiotracers designed to target tau deposition in AD, we tested a joint propagation model (JPM) to harmonize quantification (units termed "CenTauR" [CTR]). JPM is a statistical model that simultaneously models the relationships between head-to-head and anchor point data. JPM was compared to a linear regression approach analogous to the one used in the amyloid PET Centiloid scale. RESULTS: A strong linear relationship was observed between CTR values across brain regions. Using the JPM approach, CTR estimates were similar to, but more accurate than, those derived using the linear regression approach. DISCUSSION: Preliminary findings using the JPM support the development and adoption of a universal scale for tau-PET quantification. HIGHLIGHTS: Tested a novel joint propagation model (JPM) to harmonize quantification of tau PET. Units of common scale are termed "CenTauRs". Tested a Centiloid-like linear regression approach. Using five cohorts with head-to-head tau PET, JPM outperformed linearregressionbased approach. Strong linear relationship was observed between CenTauRs values across brain regions.

Advancements in APOE and dementia research: Highlights from the 2023 AAIC Advancements: APOE conference.

INTRODUCTION: The apolipoprotein E gene (APOE) is an established central player in the pathogenesis of Alzheimer's disease (AD), with distinct apoE isoforms exerting diverse effects. apoE influences not only amyloid-beta and tau pathologies but also lipid and energy metabolism, neuroinflammation, cerebral vascular health, and sex-dependent disease manifestations. Furthermore, ancestral background may significantly impact the link between APOE and AD, underscoring the need for more inclusive research. METHODS: In 2023, the Alzheimer's Association convened multidisciplinary researchers at the "AAIC Advancements: APOE" conference to discuss various topics, including apoE isoforms and their roles in AD pathogenesis, progress in apoE-targeted therapeutic strategies, updates on disease models and interventions that modulate apoE expression and function. RESULTS: This manuscript presents highlights from the conference and provides an overview of opportunities for further research in the field. DISCUSSION: Understanding apoE's multifaceted roles in AD pathogenesis will help develop targeted interventions for AD and advance the field of AD precision medicine. HIGHLIGHTS: APOE is a central player in the pathogenesis of Alzheimer's disease. APOE exerts a numerous effects throughout the brain on amyloid-beta, tau, and other pathways. The AAIC Advancements: APOE conference encouraged discussions and collaborations on understanding the role of APOE.

Liquen plano ampolloso en la edad pediátrica, una adecuada respuesta al tratamiento con esteroide oral / Bullous lichen planus in children, an adequate response to treatment with oral steroid / Liquen plano bolhoso na idade pediátrica resposta adequada ao tratamento com esteróides por via oral

El liquen plano es una erupción pápulo-escamosa de la cual se han descrito numerosas variantes en su presentación clínica. Una de esas variantes es el liquen plano ampolloso, en la que se desarrollan vesículas y ampollas que se originan de las pápulas características del liquen plano, o rara vez, de piel de aspecto normal. Debido a la formación de ampollas, el diagnóstico diferencial incluye liquen plano penfigoide, penfigoide ampolloso, pénfigo vulgar, eritema multiforme e infección por virus del herpes, por lo tanto, el examen histopatológico es útil para el diagnóstico definitivo. Las opciones de tratamiento incluyen esteroides tópicos y sistémicos, retinoides sistémicos, fototerapia, antimaláricos y agentes inmunosupresores. Se presenta el caso de una niña con diagnóstico clínico de liquen plano ampolloso que fue confirmado por histopatología, destacando la importancia de conocer esta rara variante y demostrando la adecuada respuesta al tratamiento con esteroides orales.

Lichen planus is a papulosquamous eruption whith numerous clinical variants. One of these variants is bullous lichen planus in which vesicles and blisters develop originating from lichen planus papules, or rarely in normal-looking skin. Due to formation of blisters, differential diagnosis includes lichen planuspemphigoid, bullous pemphigoid, pemphigus vulgaris, erythema multiforme and herpes virus infection, therefore histopathological examination is essential for a definitive diagnosis. Teatment includes topical and systemic steroids, systemic retinoids, phototherapy, antimalarials and immunosuppressive agents. We report the case of a child with clinical diagnosis of bullous lichen planus confirmed by histopathology,emphazise the importance of this rare variant and demonstrating the adequate response to treatment with oral steroid.

O líquen plano é uma erupção papulo-escamosa com numerosas variantes em sua apresentação clinica. Dessas variantes clínicas, uma é o líquen plano bolhoso, onde vesículas e bolhas originam- -se das papulas características do líquen plano, ou raramente, na pele de aparência normal. Devido à formação de bolhas, o diagnóstico diferencial inclui líquen plano penfigóide, penfigoide bolhoso, pênfigo vulgar, eritema multiforme e infecção pelo vírus do herpes, por isso, o exame histopatológico é útil para o diagnóstico definitivo. As opções de tratamento incluem esteróides tópicos e sistêmicos, retinóides sistêmicos, fototerapia, antimaláricos e imunossupressores. O caso de uma criança com diagnóstico clínico de líquen plano bolhoso foi confirmado por histopatológia , é apresentado com destaque para a importância de conhecer esta variante rara e demonstrando resposta adequada ao tratamento com esteróides orais.

Efecto apoptótico in vivo del interferon alfa-2B (IFN) sobre hígados preneoplásicos de rata / In vivo apoptotic effect of alpha-2B interferon (IFN) on rat preneoplastic liver

Para conocer si el IFN a previene la oncogenesis in vivo, en estadíos tempranos del desarrollo tumoral, evaluamos la acción del IFN a-2b sobre focos preneoplásicos en hígado de rata. Los animales se dividieron en los siguientes grupos: sujetos a un modelo de iniciación-promoción (G1), tratados con IFN a-2b durante: a) iniciación-promoción (G2), b) iniciación (G3), c) promoción (G4); sujetos solo al estadío de iniciación (G5) y tratados con IFNa-2b en este período (G6). El área y el número de los focos preneoplásicos rGST P-positivos se mostraron significativamente disminuidos y el Indice Apoptótico aumentado en los G2, 3 y 6. Los niveles de Bcl-2 y Bcl-xL están disminuidos en los grupos tratados con IFN a-2b y los de Bax mitocondrial aumentados en los G2, 3 y 6. En conclusión, los hepatocitos preneoplásicos de ratas que recibieron IFN a-2b sufren muerte celular programada como resultado de un aumento sustancial de Bax y de su translocación a la mitocondria.

Efecto apoptótico in vivo del interferon alfa-2B (IFN) sobre hígados preneoplásicos de rata / In vivo apoptotic effect of alpha-2B interferon (IFN) on rat preneoplastic liver

Para conocer si el IFN a previene la oncogenesis in vivo, en estadíos tempranos del desarrollo tumoral, evaluamos la acción del IFN a-2b sobre focos preneoplásicos en hígado de rata. Los animales se dividieron en los siguientes grupos: sujetos a un modelo de iniciación-promoción (G1), tratados con IFN a-2b durante: a) iniciación-promoción (G2), b) iniciación (G3), c) promoción (G4); sujetos solo al estadío de iniciación (G5) y tratados con IFNa-2b en este período (G6). El área y el número de los focos preneoplásicos rGST P-positivos se mostraron significativamente disminuidos y el Indice Apoptótico aumentado en los G2, 3 y 6. Los niveles de Bcl-2 y Bcl-xL están disminuidos en los grupos tratados con IFN a-2b y los de Bax mitocondrial aumentados en los G2, 3 y 6. En conclusión, los hepatocitos preneoplásicos de ratas que recibieron IFN a-2b sufren muerte celular programada como resultado de un aumento sustancial de Bax y de su translocación a la mitocondria. (AU)