Basic Science and Pathogenesis.

Background: Alzheimer's Disease (AD) is a neurodegenerative proteinopathy in which Aβ can misfold and aggregate into seeds that structurally corrupt native proteins, mimicking a prion-like process. These amyloid aggregation and propagation processes are influenced by three factors: the origin of the Aβ seed, time of incubation and host. However, the mechanism underlying the differential effect of each factor is poorly known.

Basic Science and Pathogenesis.

Background: The increased vulnerability of Alzheimer's disease patients to severe SARS-CoV-2 infection raises crucial concerns, especially with the potential transition of the COVID-19 pandemic to an endemic state. Given the rising prevalence of Alzheimer's in an aging world-wide population, elucidating whether SARS-CoV-2 infection may induce or accelerate neurodegeneration becomes imperative.

Method: To investigate the neurodegenerative effects of SARS-CoV-2 infection, we generated brain organoids using human induced pluripotent stem lines from one non-demented control, one with sporadic Alzheimer's, and one with familial Alzheimer's.

Basic Science and Pathogenesis.

Background: An elevated neutrophil-lymphocyte ratio (NLR) has been associated with Alzheimer's disease (AD). However, an elevated NLR has also been implicated in many other conditions that are risk factors for AD, prompting investigation into whether the NLR is directly linked with AD pathology or a result of underlying comorbidities.

Method: We explored the relationship between the NLR and AD biomarkers in the cerebrospinal fluid (CSF) of cognitively unimpaired (CU) subjects.

Basic Science and Pathogenesis.

Background: Murine studies have identified blood proteins that influence brain aging, but translating these findings to humans remains challenging. We used an innovative approach to investigate whether genetically predicted blood levels of proteins linked to brain aging in animal models are associated with cognitive performance in individuals at risk of Alzheimer's disease (AD) [Figure 1].

Method: Through systematic review, we identified 13 circulating proteins with an aging/rejuvenating effect on the mouse brain.

Integrated Analysis of Methylome and Transcriptome Responses to Exercise Training in Children with Overweight/Obesity.

We examined the effects of a 20-week exercise intervention on whole-blood genome-wide DNA methylation signature and its association with the exercise-induced changes in gene expression profiles in boys and girls with overweight/obesity (OW/OB). Twenty-three children (10.05 ± 1.

Basic Science and Pathogenesis.

Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare, hereditary cerebrovascular disease which causes stroke, complex migraine, and cognitive impairment. Given its monogenic nature, CADASIL is considered a 'pure' model of small vessel disease and vascular dementia. CADASIL is caused by NOTCH3 pathogenic variants with a broad resulting phenotypic spectrum.

Basic Science and Pathogenesis.

Background: Preclinical Alzheimer's disease may be linked to impaired cerebral amyloid clearance. We aim to obtain dynamic parameters of cortical and ventricular clearance of C-PIB and compare them with CSF amyloid values in a population of healthy volunteers.

Method: We evaluated 8 healthy volunteers (4 men and mean age: 64.

Basic Science and Pathogenesis.

Background: The accumulation of misfolded tau proteins, an Alzheimer's disease (AD) hallmark, starts decades before the emergence of cognitive decline and clinical diagnosis. Autopsy studies support a predictable progression of tau pathology through large-scale systems. However, less is known about the specific progression patterns.

Basic Science and Pathogenesis.

Background: Autosomal dominant progranulin (GRN) mutations are a common genetic cause of frontotemporal lobar degeneration. Though clinical trials for GRN-related therapies are underway, there is an unmet need for biomarkers that can predict symptom onset and track disease progression. We previously showed that presymptomatic GRN carriers exhibit thalamocortical hyperconnectivity that increases with age when they are presumably closer to symptom onset.

Basic Science and Pathogenesis.

Background: Alzheimer's (AD) and Parkinson's disease (PD) feature progressive neurodegeneration in a remarkably regionally selective manner. Post mortem studies have posited a role for cell autonomous mechanisms driving this, so we aimed to examine a live human induced pluripotent stem cell (iPSC) model to see whether it can replicate the phenomenon of selective neuronal vulnerability, so to better determine disease mechanisms and therapeutic targets.

Method: iPSC-derived neurons offer a rare opportunity to examine cell autonomous vulnerability in live human cells.

Basic Science and Pathogenesis.

Background: Despite being the most common cause of dementia worldwide, the mechanisms underlying the progression of Alzheimer's disease (AD) are not clear and effective treatments are still needed. Hence, further investigation regarding the pathogenesis of AD is required, which might allow for a better understanding of the disease, as well as for an early diagnosis of AD, thus improving the clinical management of AD patients. Here, to identify key proteins in AD pathogenesis, we performed two proteomics strategies, TMT (Tandem Mass Tags) 10-plex quantitative proteomics and LFQ (Label Free Quantification).

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) is a complex disorder and multiple cellular and molecular mechanisms are involved in AD onset and progression. Recent evidences have suggested that metabolic alterations are an important pathological feature in disease progression in AD. Likewise, diabetes and obesity, two mayor metabolic illnesses, are risk factors for AD.

Basic Science and Pathogenesis.

Background: We recently developed a novel tau-PET summary measure THETA, capturing regional heterogeneity and identifying tau status, using ground truth visual assessments from a large single-center cross-sectional dataset and validated on independent cohorts [1, 2]. In this study, we aimed to evaluate the performance of THETA on longitudinal and histopathology data.

Method: We included longitudinal tau-PET ([F]flortaucipir) data from 696 Mayo Clinic Study of Aging (MCSA) and ADRC participants, with histopathology in n = 90.

Basic Science and Pathogenesis.

Background: Transcriptomic and pathological studies indicate that microglia play a key role in the progression of Alzheimer's disease (AD). Throughout the stages of the AD continuum, there may be varying microglia phenotypes, such as the disease-associated microglia (DAM). Microglia proteins have been detected in cerebrospinal-fluid (CSF), providing a quantifiable avenue for potential stage-detection.

Basic Science and Pathogenesis.

Background: Synaptic degeneration is a primary neuropathological factor associated with cognitive decline in Alzheimer's disease (AD). In 2021, we generated a synaptic Polygenic Risk Score (PRS) that comprised only 8 variants within 6 synaptic genes (APOE, PICALM, BIN1, PTK2B, DLG2 and MINK1) that predicted AD with 72% accuracy in two neuropathological cohorts. This supports the hypothesis that genetic variants that regulate an individual's vulnerability to AD-related synapse degeneration could be used to identify individuals at-risk for AD prior to the appearance of clinical symptoms.

Basic Science and Pathogenesis.

Background: Synapse degeneration is one of the earliest changes in Alzheimer's disease (AD) and is the major neuropathologic correlate of cognitive impairment. The aim of this study was to characterize microRNA (miRNA) dysregulation at AD synapses post-mortem brain tissue and explore the specificity for AD.

Method: We prepared synaptosomes (SYN) by serial ultracentrifugation of 10 AD (mean age = 77.

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.

Clustering patients with COVID-19 according to respiratory support requirements, and its impact on short- and long-term outcome (RECOVID study).

Introduction: The Spanish Society of Pulmonology and Thoracic Surgery created a registry for hospitalised patients with COVID-19 and the different types of respiratory support used (RECOVID). Objectives. To describe the profile of hospitalised patients with COVID-19, comorbidities, respiratory support treatments and setting.

Clinical Manifestations.

Background: Subjective Cognitive Decline (SCD) may represent the initial symptom of Alzheimer's disease (AD), but SCD may be absent and/or unrelated to actual cognitive decline. Objective Subtle Cognitive Decline (obj-SCD) can be identified through longitudinal standardized neuropsychological tests in individuals not yet meeting criteria for Mild Cognitive Impairment (MCI). We argue that the relationship between SCD and obj-SCD might help to inform clinical and research criteria in pre-MCI stages.

Clinical Manifestations.

Background: The importance of coincidence of cognitive complaints between participants without objective impairment and their informants in predicting progression remains unclear (Nosheny et al, 2022). Our objective was to determine whether agreement in dyadic reporting at baseline can predict survival time to progression to MCI or dementia.

Method: A sample of 145 participants from the CompAS Study was included in a survival analysis.

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: Practice effects are a well-known cognitive phenomenon that is reduced in patients with Alzheimer's disease (AD). We aimed to investigate whether cognitively unimpaired (CU) individuals within the Alzheimer's continuum (i.e.

Clinical Manifestations.

Background: Neuromodulatory subcortical systems (NSS) are affected from the early stages of Alzheimer's Disease (AD) by the accumulation of tau pathology. Increased tau burden within the subcortical nucleus that are in control of sleep and wake regulation may contribute to the breakdown of sleep-wake patterns in AD. A recent postmortem study showed that subcortical wake-promoting neurons were related to sleep phenotypes in AD and PSP, being that greater neuronal count in locus coeruleus (LC), tuberomammillary nucleus (TMN), and lateral hypothalamic area (LHA) associated with a decreased sleep drive (Oh et al.

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.