Basic Science and Pathogenesis.

Background: The microtubule-associated protein tau is the most commonly misfolded protein in neurodegenerative disorders including Alzheimer's disease and other related tauopathies. These neurological illnesses are hypothesized to share a common mechanism of disease progression, where pathogenic aggregates or 'seeds' of the tau protein function as templates promoting misfolding of functional, soluble tau protein. Under this premise, therapeutic strategies that modulate the seeding cascade, have high potential to interfere with the disease process.

Basic Science and Pathogenesis.

Background: Genetic variations have emerged as crucial players in the etiology of Alzheimer's disease (AD), and they serve for a better understanding of the disease mechanisms; yet the specific roles of these genetic variants remain uncertain. Animal models with reminiscent disease pathology could uncover previously uncharacterized roles of these genes. Therefore, we generated zebrafish models for AD variants to analyze the in depth molecular and biological functions of these variants.

Basic Science and Pathogenesis.

Background: Western-diet (WD) can induce sterile inflammation and epigenetic reprogramming of myeloid cells, affecting their immune response (Christ et al., 2018). However, the molecular signaling mediating these changes was unknown.

Basic Science and Pathogenesis.

Background: As neurodegenerative diseases advance, postmitotic neurons are affected by disturbed proteostasis and the accumulation of misfolded proteins. This renders neurons sensitive to cell death, ultimately leading to progressive neuron loss. Multiple studies show the involvement of distinct pathways of regulated cell death (RCD) in neurodegenerative diseases, such as necroptosis.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD), an untreatable synaptic disorder, is the most frequent cause of dementia. It is still unclear which mechanisms drive the early synapse dysfunction in the most common late-onset AD (LOAD). The second most important LOAD risk gene identified, BIN1, is an endocytic regulator.

dEREGulated pathways: Unraveling the role of epiregulin in skin, kidney and lung fibrosis.

The epidermal growth factor receptor (EGFR) signaling pathway is an evolutionary conserved mechanism to control cell behavior during tissue development and homeostasis. Deregulation of this pathway has been associated with abnormal cell behavior, including hyperproliferation, senescence, and an inflammatory cell phenotype, thereby contributing to pathologies across a variety of organs, including kidney, skin, and lung. To date, there are seven distinct EGFR ligands described.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) brains commonly exhibit various co-morbid pathologies, with cerebral amyloid angiopathy (CAA) being the most prevalent, affecting 70-90% of patients. CAA can be restricted to medium and large vessels or extend to capillaries. Additionally, AD patients often show pathologies involving phosphorylated-TDP-43 (pTDP-43) and alpha-synuclein (αSyn), typically demonstrating an amygdala-predominant subtype.

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: 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: Alzheimer's disease (AD) is a heterogenous disease with a strong heritability. Genetic studies are of irreplaceable value in elucidating the mechanisms that underly this disease. The classical genome-wide association studies (GWAS) rely on ever-increasing sample sizes and utilize clinical AD diagnosis to investigate genetic risk.

Basic Science and Pathogenesis.

Background: Neuroimaging studies have revealed age and sex-specific differences in Alzheimer's disease (AD) trajectories. However, how age and sex modulate tau spreading remains unclear. Thus, we investigated how age and sex modulate the amyloid-beta (Aβ)-induced accumulation and spreading of tau pathology from local epicenters across connected brain regions.

Clinical Manifestations.

Future clinical trials targeting Alzheimer's disease (AD) on new disease modifying drugs necessitate a paradigm shift towards early identification of individuals at risk. Emerging evidence indicates that subtle alterations in language and speech characteristics may manifest concurrently with the progression of neurodegenerative disorders like AD. These changes manifest as discernible variations, assessable through semantic nuances, word choices, sentiment, grammar usage (linguistic features), and phonetic/acoustic traits (paralinguistic features).

Clinical Manifestations.

Background: Subjective cognitive decline (SCD) is a condition, where individuals report persistent decline of cognitive abilities, even though this decline is not detectable by neuropsychological screenings. Individuals with SCD are at a higher risk of suffering from mild cognitive impairment (MCI) and Alzheimer's disease (AD) in the future. It is important to better understand SCD to develop prevention measures, before a transition from a possible preclinical stage to MCI and AD.

Clinical Manifestations.

Background: Changes in speech and language functions have shown to be early symptoms of AD pathology. Recent developments in automatic speech and language processing have opened avenues for objective assessments of these changes. The primary objective of this study is to explore whether speech and language markers extracted from cognitive testing conducted during an automated phone call differ according to underlying AD pathology as measured in cerebrospinal fluid (CSF) in preclinical or early stage individuals.

Clinical Manifestations.

Background: Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a neuropathologically-defined disease, and it is frequently comorbid with Alzheimer's disease neuropathological change (ADNC). However, the neurological syndrome associated with LATE neuropathological change (LATE-NC) is not defined. We propose a set of clinical criteria for a limbic-predominant amnestic neurodegenerative syndrome (LANS) that is highly associated with LATE-NC.

Clinical Manifestations.

Background: In cognitively unimpaired (CU) older adults, the presence of a subjective cognitive decline (SCD) combined with evidence of abnormal b-amyloid (Ab) is proposed as stage 2 of Alzheimer's disease (AD) by the NIA-AA framework (Jack et al., 2018). However, the associations found between SCD and preclinical AD are inconsistent across studies, highlighting the importance of better understanding which specific SCD features are associated with either Ab or tau burden.

Clinical Manifestations.

Background: The medial temporal lobe (MTL) is the first cortical region affected by tauopathy in Alzheimer's disease (AD) and is implicated in spatial orientation. In early AD stages, navigation deficits, including path integration deficits, could be present, even before memory deficits. We investigated whether these deficits were related to AD pathology (amyloidosis and/or tauopathy) using a path integration task, the "Apple Game".

Clinical Manifestations.

Background: Remote unsupervised cognitive assessments have the potential to complement and facilitate cognitive assessment in clinical and research settings.

Method: Here we evaluate the usability, validity and reliability of unsupervised remote memory assessments via mobile devices (see Figure 1) in individuals without dementia from the Swedish BioFINDER-2 study and explore their prognostic utility regarding future cognitive decline in combination with a plasma marker for p-tau217.

Result: Usability was rated positively.

Clinical Manifestations.

Background: Speech and language impairments are associated with cognitive decline in neurodegenerative dementias, particularly Alzheimer's Disease (AD), where subtle speech changes may precede clinical dementia onset. As clinical trials prioritize early identification for disease-modifying treatments, digital biomarkers for timely screening become imperative. Digital speech-based biomarkers can be employed for screening populations at the earliest AD stages.

The Effect of Novel Laser-Activated Bleaching Protocols on the Color Change of Non-Vital Anterior Teeth: An In Vitro Study.

Objective:  This study compares the color change of non-vital anterior teeth after laser-activated bleaching and conventional walking bleaching technique.

Materials And Methods:  Sixty extracted teeth were endodontically treated, stained in a black tea solution, and the baseline shade was measured using a spectrophotometer (Easyshade, VITA). Bleaching was done using either: internal bleaching with 35% HO (Opalescence Endo) and then tooth sealed for 5 days (Gr1), 35% HO (JW Next) for 7 minutes (Gr2), internal and external bleaching for 7 minutes (Gr3), diode laser-activated internal bleaching for 30 seconds (940 nm, continuous wave, 2 W, noncontact mode, 300 um, non-initiated tip), wait for 7 minutes, second laser application for 30 seconds, tooth sealed for 5 days (Gr4), diode laser-activated internal bleaching for 24 hours (Gr5), or diode laser-activated internal and external bleaching for 24 hours (Gr6) ( = 10).

Beverage-Induced Surface Changes in Biomimetic Dental Resin Composite: AFM and Bacterial Analysis.

Objective:  Continuous advancements in composite resin materials have revolutionized and expanded its clinical use, improving its physical and mechanical properties. Attaining and retaining surface texture and gloss are crucial for the long-term durability of the composite resin material. This study investigated the supra-nanospherical filler composite material compared with different composite resin materials immersed in different beverages.

Clinical Manifestations.

Background: Anosognosia is a frequent phenomenon in Alzheimer's dementia. Both heightened and decreased awareness of cognitive decline (AoCD) have been observed in mild cognitive impairment (MCI) and subjective cognitive decline (SCD). Despite some studies, the association between altered awareness and clinical conversion remained unclear.

Clinical Manifestations.

Background: Judgment is an aspect of executive functioning that is critical to many aspects of daily functioning, and often affected in older adults with cognitive decline. The Test of Practical Judgement (TOP-J) evaluates judgment related real-world issues that may arise in aging populations. The current study investigates the incremental validity of the TOP-J-i.

Clinical Manifestations.

Background: Previous findings evaluating longitudinal cognition in relation to the MeDi diet are inconsistent, and few studies have examined it in relation to the presence/absence of subjective cognitive decline (SCD). Our current aims are to test whether adherence to the MeDi diet is associated with the risk of clinical progression, future cognitive decline, and atrophy over time in Alzheimer's disease (AD)-sensitive regions in cognitively unimpaired (CU) older adults with or without SCD.

Methods: This longitudinal study includes 171 controls and 228 SCD patients recruited from memory clinics in the DELCODE study.

Clinical Manifestations.

Background: Traditional pen-and-paper neuropsychological assessments fail to capture subtle cognitive changes in the early stages of Alzheimer's disease (AD). Remote and unsupervised digital assessments available on smartphones, tablets, and personal computers may offer a solution to this by increasing the amount and types of data available to researchers and clinicians, while simultaneously improving ecological validity and alleviating patient burden. As these remote and unsupervised digital cognitive assessment tools become more widely available, it is important that they are validated in a systematic way.