Basic Science and Pathogenesis.

Background: The apolipoprotein ε4 (ApoE4) allele is a major risk factor for sporadic Alzheimer's disease (AD) and was shown to promote amyloid-β (Aβ) accumulation and mediate pathophysiological processes in AD. Although the molecular interaction between Aβ and ApoE is acknowledged, the precise nature of this interaction remains unclear. This study aims to explore the biophysical and biochemical nature of the interaction between Aβ and ApoE in the ε3 and ε4 isoforms.

Basic Science and Pathogenesis.

Background: Recent research has demonstrated that the consumption of high fat diet (HFD) can lead to metabolic dysfunctions and cognitive impairments in both mice models and humans. Given the potential negative effects of HFD, it is crucial to explore non-pharmacological alternatives that can serve as a potential treatment for both metabolic dysfunctions and behavioral effects induced by HFD. Therefore, the aim of this study is to assess the impact of chronic and intermittent exposure to cold temperature on the metabolic and cognitive changes associated with HFD consumption.

Basic Science and Pathogenesis.

Background: Alzheimer's Disease(AD) patients experience circadian rhythm disorder. The circadian rhythm is synchronized by a master clock, the suprachiasmatic nucleus(SCN), which is spatially well-conserved but a tiny nucleus in the hypothalamus. Little is known about the molecular and pathological changes that occur in the SCN during AD progression.

Basic Science and Pathogenesis.

Background: In Alzheimer's disease (AD) the fact that neuropsychiatric symptoms can predate the onset of cognitive symptoms suggests that greater focus on the non-cognitive behavioral changes in earlier life could be an opportunity to investigate 'latent' mild behavioral impairment (MBI) as a possible diagnostic strategy for preclinical AD.

Method: We used 1- and 6-month-old 3xTg-AD male mice and age-matched wild-type animals (CEUA-ICB/USP: 127/2015). Two batteries of behavioral tests were performed: (1) open field test (OFT), novel object recognition test (NORT), and rotarod test; (2) elevated zero maze test (EZMT), forced swim test (FST), and sucrose preference test (SPT).

Basic Science and Pathogenesis.

Background: Physical exercise has been proposed as an approach to reduce the risk of Alzheimer's disease (AD). Engaging in physical exercise triggers the shedding of the extracellular domain of fibronectin type III domain-containing protein 5 (FNDC5), producing a circulating peptide (irisin) that promotes neuroprotection in AD mouse models. Despite recent evidence indicating that reduced FNDC5/irisin levels in brain and cerebrospinal fluid correlate with amyloid beta pathology, the impact of FNDC5/irisin on tau pathology remains uncertain.

Basic Science and Pathogenesis.

Background: Calcineurin, a protein involved in functions such as synaptic plasticity and neuronal survival, plays an important role in the pathophysiology of Alzheimer's disease. This study, randomized, investigated the effects of FK506 (FK), a calcineurin inhibitor, on the behavioral, histological, and biochemical alterations observed in models of neurotoxicity induced by NMDA or Aβ and in a transgenic model for AD, in addition to the organotypic culture model stimulated with NMDA.

Methods: This study involved models for AD to experiment injecting NMDA or Aβ1-42 into the hippocampus of male C57Bl/6 mice aged 8-12 weeks to induce a neurotoxicity model, treating double-transgenic APP/PS1 mice, expressing both mouse/human APP and mutant human PS1, with chronic FK506 for AD, in which, to enable NMDA or Aβ1-42 microinjections, another experiment including a stereotaxic surgery was performed on the C57Bl/6 mice.

Basic Science and Pathogenesis.

Background: Previous studies suggest an association between Alzheimer's disease and carotid artery atherosclerosis. However, the association between atherosclerotic carotid plaque composition and Alzheimer's disease pathology (neuritic plaques and neurofibrillary tangles) has not been explored yet.

Method: Carotid arteries were dissected and the segments with the largest obstruction in the carotid bifurcation, and the common and internal carotid arteries were obtained.

Basic Science and Pathogenesis.

Background: Worldwide, the actual number of 55 million people diagnosed with dementia is estimated to increase to 139 million people affected by dementia in 2050. 61% of these individuals resided in low and middle-income countries (LMIC). Genetic risk factors account for up to 80% of the attributable risk of Alzheimer's disease (AD), the leading cause of dementia.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) features stereotypical spread of hyperphosphorylated tau (p-tau) and beta-amyloid. Although other pathological tau posttranslational modifications (PTMs) have been described in AD, a prevalent disease model preconizes that other tau PTMs always coincide with p-tau, making the latter an excellent marker of pathological tau burden. We showed in experimental studies that truncated tau (tr-tau), a pathological tau PTM generated via cleavage by active caspases, is as common as p-tau in neurons at late AD stages; however, only about 40% of tr-tau positive neurons also show p-tau positivity.

Basic Science and Pathogenesis.

Background: Aging is a natural, irreversible process that can be successful or pathological, resulting in chronic degenerative diseases such as Alzheimer's disease. Low levels of estrogen characterize menopause. Research reveals that the lack of these hormones may be related to dementia and that vitamin D (vit D), when supplemented, has a neuroprotective and neuromodulator effect.

Basic Science and Pathogenesis.

Background: Replacement, Reduction, and Refinement (3R) guidelines propose the use of alternative models to study human diseases. These models have high homology and are less onerous compared to rodents, which dominate Alzheimer's disease (AD) research. However, it is still necessary to investigate whether evolutionary components are conserved among AD models cross-species.

Basic Science and Pathogenesis.

Background: Individuals with early stages of cognitive decline face a significant stagnation in their financial capacity, leading to a decrease in quality of life. However, whether changes in brain function are associated with financial capacity remains unclear. Here, we evaluate the association between financial capacity and brain glucose metabolism.

Basic Science and Pathogenesis.

Background: The Brazilian population has been experiencing an increase in the number of older adults, with a simultaneous rise in the incidence of Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD). Telomeres are structures located at the ends of chromosomes that maintain the structural integrity of the chromosome. There is a shortage of studies correlating telomeres and cognition.

Basic Science and Pathogenesis.

Background: Prior research investigating sex and racial differences in amyloid pathology burden has yielded inconsistent findings. We examined the impact of sex and other confounding factors on neuritic plaque burden and cognitive outcomes.

Method: This study included 1,857 individuals, with post-mortem brain tissues, from the Biobank for Aging Studies of the University of São Paulo Medical School, collected from 2004-2023.

Basic Science and Pathogenesis.

Background: Recent studies have suggested a transient glucose hypermetabolism in early phases of Alzheimer's Disease (AD), which is followed by a characteristic glucose hypometabolism in dementia stages. This phenomenon desveres further investigation and it is suggested to be associated to glial/inflammatory or compensatory neuronal responses. Here, we aimed to longitudinally investigate brain glucose metabolism in an AD animal model and explore associated cellular and inflammatory changes.

Basic Science and Pathogenesis.

Background: Dysregulation of cholesterol metabolism contributes to the increase of cerebral vascular diseases, favoring the development of dementia. In this sense, high levels of high-density lipoprotein (HDL) are considered protective against the outcomes associated with cardiovascular diseases. However, little is known about the effect of plasma HDL levels to alterations of cerebral volume in non-vascular AD and vascular AD individuals.

Basic Science and Pathogenesis.

Background: In recent years, researchers have linked epigenetic factors to numerous diseases, one of them being Alzheimer's Disease (AD). Those factors may lead to the disease but also serve as a path for new treatments and prevention methods.

Method: A wide selection of articles in the PubMed platform that focused on epigenetics, Alzheimer's Disease, and correlating aspects among them were reviewed.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) is characterized by the accumulation of amyloid-β (Aβ) plaques and tau tangles in the brain, and neurotransmission dysfunctions. Indeed, our group recently demonstrated that the γ-aminobutyric acid (GABA)ergic system is vulnerable to AD pathology in humans. However, whether this vulnerability is also present in AD rodent models is still unknown.

Basic Science and Pathogenesis.

Background: Understanding the molecular mechanisms underlying selective neuronal vulnerability is crucial for developing effective treatments for Alzheimer's disease (AD). Our group has shown that RORB/CDH9-positive excitatory neurons in the entorhinal cortex (EC) display selective vulnerability as early as Braak stage (BB) 2. However, not all RORB/CDH9-positive neurons are vulnerable.

Basic Science and Pathogenesis.

Background: Excessive dietary fat is not only a risk factor for metabolic disorders but also for premature cognitive decline and Alzheimer's disease. Recent findings from our study revealed that even a few days of a high-fat diet (HFD) are sufficient to disrupt hippocampal bioenergetics, activate microglia, and induce cognitive decline in mice. We hypothesize that microglia, rather than merely responding to diet-induced damage, play a critical role in disrupting synaptic homeostasis.

Basic Science and Pathogenesis.

Background: The increasing prevalence of neurodegenerative diseases, particularly among women post-menopause, is linked to the decline in 17 β estradiol (E2). Vitamin D deficiency, common in older individuals, exacerbates this risk due to its anti-inflammatory and neuroprotective properties. Hypovitaminosis D is associated with age-related conditions, including cognitive decline.

Basic Science and Pathogenesis.

Background: Transactive DNA-binding protein 43 (TDP-43) proteinopathy is associated with neurodegeneration, including LATE and linked to cognitive deterioration. While some research suggests a higher prevalence of TDP-43 in women, no differences have been identified among racial groups. Nonetheless, the influence of gender on cognition within the context of TDP-43 remains uncertain.

Basic Science and Pathogenesis.

Background: Pneumococcal meningitis is a type of meningitis that may face long-term neurological complications, leading to the hypothesis that it might contribute to the deposition of beta-amyloid (Aβ) and predispose individuals to Alzheimer's pathology.

Method: Male and female APP/PS1 mice, 50 days old, were divided into control (n = 5) and meningitis (n = 6). Under anesthesia, an intracisternal injection of either artificial cerebrospinal fluid (CSF) as a placebo or 5 × 10 colony-forming units (CFU) of S.

The True Appearance Behind Satisfaction in Young Women: A Study Using Stereophotogrammetry and FACE-Q.

This cross-sectional observational study aimed to investigate the relationship between satisfaction with facial appearance among young women, as measured by the FACE-Q tool, and facial asymmetry quantified through stereophotogrammetry. A total of 50 women aged 18 to 30 years with a normal body mass index were recruited for the study. Participants were categorized as either symmetrical or asymmetrical based on facial asymmetry assessments obtained through clinical examination and stereophotogrammetry using the Vectra M3 system.

Clinical Manifestations.

Background: The salience network (SN) functions as a dynamic switch between the default mode network (DMN) and the frontoparietal network (FPN), aligning with salience and cognitive demand. Dysfunctions in SN activity within the cognitive and affective domains are linked to a wide range of deficits and maladaptive behavioral patterns in various clinical disorders. Emotion recognition is pivotal in social interactions and can be affected in neurodegenerative disorders.