Basic Science and Pathogenesis.

Background: Alzheimer's Disease (AD) is a widespread neurodegenerative disease with Mild Cognitive Impairment (MCI) acting as an interim phase between normal cognitive state and AD. The irreversible nature of AD and the difficulty in early prediction present significant challenges for patients, caregivers, and the healthcare sector. Deep learning (DL) methods such as Recurrent Neural Networks (RNN) have been utilized to analyze Electronic Health Records (EHR) to model disease progression and predict diagnosis.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) is the memory-related neurodegenerative disorder, contributing to 70% of the cases globally. Synaptic dysfunction is a well-known early event that causes progressive cognitive decline in AD. The latest AD therapeutics on the forefront only offer a moderate symptomatic relief with significant off-target effects.

Basic Science and Pathogenesis.

Background: This study identifies and quantifies diverse pathological tau forms in the retina at both early and advanced stages of Alzheimer's disease (AD) and assesses their correlation with disease status. In the pathogenesis of AD, the tau protein undergoes post-translational modifications, including hyperphosphorylation (p-tau). As the disease progresses, pathological tau can propagate as oligomers, aggregate into fibrils, and paired helical filaments (PHF), and ultimately form intraneuronal neurofibrillary tangles (NFTs).

Basic Science and Pathogenesis.

Background: Older females, particularly susceptible to Alzheimer's disease (AD), may be affected by hormonal fluctuation during life. We aim to investigate the relationship between changes in brain volume and sex steroid hormones over time. We hypothesize that levels of sex hormones (17ß-estradiol, progesterone, and testosterone) relate to changes in brain volume, especially in the hippocampus (HPC) and cerebellum (CB).

Basic Science and Pathogenesis.

Background: During aging, we observe several changes in the brain that render it more vulnerable to a variety of age-related neurodegenerative diseases, including Alzheimer's Disease. Glia-neuron interactions mediate brain development and physiology via cell-surface proteins at the cell-surface interface, and dysregulation of these interactions is considered one of the hallmarks of brain aging. Due to the critical role glial cells play in neuroplasticity, immune function, and homeostasis, dysregulation of glial cell-surface proteins is hypothesized to contribute to neurodegeneration.

Basic Science and Pathogenesis.

Background: Chemotherapy-induced cognitive impairment (CICI) is a commonly reported neurotoxic side effect of chemotherapy, occurring in up to 75% cancer patients. Connections between chemo-treatment and increased risk of dementia have been reported. Mechanistically, chemotherapy treatment contributes to an accelerated aging phenotype in the brain through induction of pathogenic tau, disruption of neuronal integrity, reactive gliosis and neuroinflammation.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder leading to dementia. The existence of individuals who remain cognitively intact despite presenting histopathological signs of AD, here referred to as "Non-demented with AD neuropathology" (NDAN), suggests that some mechanisms are triggered to resist cognitive impairment. These individuals are distinguished by the presence of highly phagocytic microglia capable of clearing damaged synapses near plaques, mitigating further damage to axons and dendrites.

Basic Science and Pathogenesis.

Background: The oligomers and fibrils of tau are well known as an indicator of Alzheimer's disease (AD). Recently, other protein aggregates have been shown to be potentially involved in the development of the disease. One of these proteins is p53, involved in DNA repair.

Basic Science and Pathogenesis.

Background: APP duplications are a rare form of familial Alzheimer's disease (AD). Research has shown variability in clinical presentation with full duplications. There is limited information on those with partial duplications, especially in underrepresented minorities.

Basic Science and Pathogenesis.

Background: Consortium-wide studies of volumetric brain imaging measures with single-nucleotide polymorphisms (SNPs) have revealed numerous disease-risk SNPs and emphasized the significance of brain imaging phenotypes as preclinical markers (endophenotypes) for Alzheimer's disease (AD). Nevertheless, the bulk of these risk variants are in genomic regions that govern multiple genes, posing major challenges in fine-mapping strategies. Evolutionarily conserved transposable elements are master regulators of gene expression, and by studying these endogenous gene regulatory units in relation to AD endophenotypes, we aimed to better identify the disease-causal gene.

Basic Science and Pathogenesis.

Background: The efficacy of Calorie Restriction (CR) in enhancing cognition, promoting healthy aging, and extending lifespan is well-established. Yet, it remains unclear whether the apolipoprotein E (APOE) genotype, a known modifier for aging and age-related disorders, influences the beneficial effects of CR in countering aging.

Methods: To investigate this question, we utilized humanized APOE mouse models, which express APOE2, APOE3, or APOE4 alleles systematically (refer to as E2, E3, and E4 mice).

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: 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: Apolipoprotein (Apo) E4, a main susceptibility gene for Alzheimer's disease (AD) is associated with increased vascular dysfunction, amyloid pathology, and neurodegeneration. The effector pathways leading to increased vascular risk in ApoE4 carriers needs to be established. Platelet aggregation is a key marker of vascular dysfunction and studies need to examine whether a relationship of ApoE4 allele status and platelet biology exists METHOD: We examined cross-sectional associations of platelet aggregation with ApoE genotypes (E2 or E4 against E3, the most common) in middle-aged cognitively normal participants at the Framingham Heart Study (FHS) Gen3, New Offspring Spouse (NOS), and Omni2 Cohorts.

Basic Science and Pathogenesis.

Background: Cellular senescence, which can cause significant changes in morphology, metabolism, and function, is a key contributor to aging and diseases including Alzheimer's Disease (AD). Accurate biomarker identification is essential for detecting senescent cells. Our research aims at defining gene signatures that encapsulate senescence complexity in the brain.

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: TDP-43 is a multifunctional heterogeneous nuclear ribonucleoprotein and is the major pathological protein in motor neuron disease. Previously, TDP-43 pathology has been described in up to 50% of those with Alzheimer's disease. Recent evaluation of this cohort revealed a distinct pathological staging of TDP-43 proteinopathy in an aged population, called Limbic predominant age-related TDP-43 encephalopathy (LATE).

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.

Basic Science and Pathogenesis.

Background: Aging, tau pathology, and chronic inflammation in the brain play crucial roles in neuroinflammation, synaptic loss, neurodegeneration, and cognitive decline in tauopathies, such as Alzheimer's disease. However, the molecular mechanisms that trigger aberrant chronic inflammatory signaling in tauopathies are poorly understood.

Method: We utilized brain tissues from tauopathy patients and the tauopathy mouse models.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) is a neurogenerative disease that affect millions worldwide with no effective treatment. Several studies have been conducted to decipher to genomic underpinnings of AD. Due to its complex nature, many genes have been found to be associated with AD.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) is characterized by the accumulation of tau protein in the brain, which forms neurofibrillary tangles and contributes to the gradual deterioration of brain function. As a consequence, cellular senescence occurs, leading to cognitive impairment and hastening the aging process. Immunotherapies targeting Aβ and other protein aggregates are also being developed in the meantime.

Development of a reference standard to assign bacterial versus viral infection etiology using an all-inclusive methodology for comparison of novel diagnostic tool performance.

Background: Diagnostic test evaluation requires a reference standard. We describe an approach for creating a reference standard for acute infection using unrestricted adjudication and apply it to compare biomarker tools.

Methods: Adults and children with suspected acute infection enrolled in three prospective studies at emergency departments and urgent cares were included.

Basic Science and Pathogenesis.

Background: Clear sex differences exist in AD and PD. Several studies examined genetic regulations for AD phenotypes and gene expression data in a sex-specific manner, identifying some differences between males and females. In contrasts, although proteins are final effectors of most physiological pathways and important drug targets, sex-specific regulations for proteins remain vastly understudied.

Clinical Manifestations.

Background: Older adults increasingly rely on digital technologies to perform instrumental activities of daily living (iADLs), including commerce, managing accounts online, using texting and websites for social connection, and accessing health services via web platforms. Despite the increasingly central role of technology to daily life, current iADL measures do not regularly capture the digital approach to daily activities. The current study had three broad aims 1) determine the applicability of technology-based iADLs to the daily lives of older adults being evaluated for Alzheimer's disease and related dementias (ADRD), 2) compare the level of dependence for tech and traditional iADL items, and 3) determine if adding technology related iADL items improves the diagnostic accuracy of iADL assessments.

Clinical Manifestations.

Background: The progression of Alzheimer's disease and related dementias (ADRDs) from prodromal state to dementia syndrome prompts researchers to identify early markers of cognitive decline. One potential risk marker is subjective memory concerns (SMCs). Individuals with greater perceived stress often report more cognitive concerns.