Basic Science and Pathogenesis.

Background: Autosomal dominant Alzheimer's Disease (ADAD) represents around 0.5% of all AD cases, and is caused by mutations in PSEN1, PSEN2 and APP genes. Gene expression studies can be useful for unravelling the physiopathology of AD and identifying potential biomarkers.

Basic Science and Pathogenesis.

Background: Published data have highlighted associations between Alzheimer's disease (AD) susceptibility loci and AD-related brain changes. The amyloid imaging to prevent AD (AMYPAD) consortium is a European collaboration consisting of several parent cohorts, four of which had raw genotype array data available. We sought to integrate and harmonise the genetic data, calculate AD polygenic risk scores (PRS), and investigate their association with global amyloid deposition.

Basic Science and Pathogenesis.

Background: Down syndrome (DS) is strongly associated with Alzheimer's disease (AD), attributable to APP overexpression, displaying common features with early-onset AD (EOAD) and late-onset AD (LOAD) like Amyloid-β (Aβ) and tau pathology. Here, we evaluated the Aβ plaques proteome of DS, EOAD and LOAD.

Method: We used unbiased localized proteomics to analyze amyloid plaques and the adjacent plaque-devoid tissue ('AD non-plaque') from post-mortem paraffin-embedded tissues in three subtypes of AD (n = 20/group): DS (59.

Basic Science and Pathogenesis.

Background: Epigenetic mechanisms as a potential underlying pathogenic mechanism of neurodegenerative diseases have been the scope of several studies performed so far. However, there is a gap in analyzing different forms of early-onset dementia to minimize the effect of aging and the use of Lymphoblastoid cell lines (LCLs) as a possible disease model for earlier clinical phases.

Method: We performed a genome-wide DNA methylation analysis in 64 samples (from prefrontal cortex and lymphoblastoid cell lines) from Alzheimer's Disease (AD) and Frontotemporal dementia (FTD) using the Illumina Infinium MethylationEPIC V2.

Basic Science and Pathogenesis.

Background: In-vivo magnetic resonance imaging (MRI) has recently shown that patients with clinically diagnosed Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) exhibit degeneration of the cholinergic nucleus basalis of Meynert and its white matter (WM) projections through the cingulum and external capsule pathways. Here, we propose an imaging-pathologic validation study aimed at investigating cholinergic WM pathways using post-mortem MRI of autopsy-confirmed AD, Lewy body dementia (LBD), and other neurodegenerative diseases (OTH).

Method: We included 53 brain donors (34 AD, 10 LBD, and 9 OTH, mainly including frontotemporal lobe degeneration and vascular disease, Table 1).

Basic Science and Pathogenesis.

Background: Current evidence suggests that hippocampal subfields have partially different genetic architecture and may improve the sensitivity of the detection of Alzheimer's disease (AD). In this study, we investigated whether genetic predisposition to AD contributes to the accelerated rate of hippocampal volume atrophy across sex and AD stages and how this contribution is specifically driven by functional variants located in the APOE gene.

Methods: The study comprised 1,051 participants from ADNI cohort (75.

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.