Sex differences in brain glucose metabolism in alzheimer's disease: A voxel-based study.

A growing body of evidence shows significant sex differences in Alzheimer's Disease (AD) epidemiology, clinical presentation, and pathology burden; however, sex differences in neuroimaging biomarkers remain underexplored, prompting recent calls to action for more targeted research in this field. We analyzed static brain positron emission tomography (PET) imaging with 2-[F] fluoro-2-deoxy-D-glucose (FDG) from 247 elderly individuals with AD dementia, including 151 women and 96 men. Voxel-based analysis was used to detect reductions in FDG uptake in each sex relative to a publicly shared normative database and to identify sex differences in FDG uptake within the AD cohort.

Gender differences in cognitive reserve: An impact on progression in subjective cognitive decline?

Introduction: This study investigated gender differences in cognitive reserve (CR) in subjective cognitive decline (SCD) and examined the impact of gender-CR interaction on the risk of progression to mild cognitive impairment (MCI).

Methods: We enrolled 440 SCD patients and estimated CR using premorbid intelligence ( [TIB]). To account for socio-cultural differences, patients were stratified by birth cohort (pre-/post-1950).

The HTT gene influences plasma neurofilament light chain and brain metabolism in prodromal Alzheimer's disease.

Objective: HTT, encoding a protein involved in axonal trafficking, contains a key region of CAG repeats. When expanded beyond 39 repeats, this region leads to Huntington's disease (HD). However, several studies have suggested that increasing the number of CAG repeats below the pathological threshold may confer functional advantages by enhancing HTT activity.

Polygenic Hazard Score for Predicting Age-associated Risk of Alzheimer's Disease in European Populations: Development and Validation.

Objectives: Polygenic hazard score (PHS) models can be used to predict the age-associated risk for complex diseases, including Alzheimer's disease (AD). In this study, we present an improved PHS model for AD that incorporates a large number of genetic variants and demonstrates enhanced predictive accuracy for age of onset in European populations compared to alternative models.

Methods: We used the genotyped European Alzheimer & Dementia Biobank (EADB) sample (n=42,120) to develop and evaluate the performance of the PHS model.

Beyond language: empathy and emotion recognition deficits in primary progressive aphasias.

Although primary progressive aphasia (PPA) is considered a language disorder, increasing evidence points to the presence of social cognition impairments in PPA variants. The aims of this study were to explore empathy and emotion recognition deficits in the three PPA variants (sv-PPA, lv-PPA, nfv-PPA) and to identify their neural correlates. Eleven sv-PPA, 34 lv-PPA,11 nfv-PPA patients and 34 healthy controls (HC) were included in this study.

Machine learning in Alzheimer's disease genetics.

Traditional statistical approaches have advanced our understanding of the genetics of complex diseases, yet are limited to linear additive models. Here we applied machine learning (ML) to genome-wide data from 41,686 individuals in the largest European consortium on Alzheimer's disease (AD) to investigate the effectiveness of various ML algorithms in replicating known findings, discovering novel loci, and predicting individuals at risk. We utilised Gradient Boosting Machines (GBMs), biological pathway-informed Neural Networks (NNs), and Model-based Multifactor Dimensionality Reduction (MB-MDR) models.

Modulation of mitochondrial quality control through autophagic pathway in familial Alzheimer's disease.

Autophagy is a highly conserved cellular catabolic process recognized as an essential pathway for the maintenance of cellular homeostasis. Growing evidence implicates autophagic dysfunction in the pathogenesis of several neurodegenerative disorders, including Alzheimer's disease (AD), thus its modulation might represent an interesting therapeutic tool. Searching for a compound that stimulates autophagic pathway, led us to identify the inhibitor of RPSA receptor, NSC47924.

Analysis of short tandem repeats linked to polyglutamine diseases from whole-genome sequencing reveals intermediate alleles of associated with an early disease onset in carriers.

Carriers of the GGGGCC pathogenic expansion in can develop symptoms of frontotemporal dementia and/or amyotrophic lateral sclerosis, with variable and unpredictable ages at onset. Previous studies aiming to decipher the genetic bases of the clinical variability in this rare disease included bi-allelic polymorphisms, excluding short tandem repeats. Whole-genome sequencing data of 195 patients were used to consider all short tandem repeats linked to polyglutamine disorders as potential genetic modifiers given the existing links between and polyglutamine diseases.

Transferability of European-derived Alzheimer's disease polygenic risk scores across multiancestry populations.

A polygenic score (PGS) for Alzheimer's disease (AD) was derived recently from data on genome-wide significant loci in European ancestry populations. We applied this PGS to populations in 17 European countries and observed a consistent association with the AD risk, age at onset and cerebrospinal fluid levels of AD biomarkers, independently of apolipoprotein E locus (APOE). This PGS was also associated with the AD risk in many other populations of diverse ancestries.

"Assessing relationship between blood MAPT methylation levels and clinical expression in Frontotemporal Dementia".

Introduction: Little is known regarding the relationship between methylation levels and Frontotemporal Dementia (FTD).

Objective: The objective of the present study was to assess the relationship between blood MAPT methylation levels and clinical expression in FTD.

Methods: This cross-sectional observational study was conducted including 54 Italian patients with different phenotypes: 22 behavioral variant FTD (bvFTD), 10 semantic variant (svPPA), 22 non-fluent variant (nfv) Primary Progressive Aphasia (PPA).

Digital twins and non-invasive recordings enable early diagnosis of Alzheimer's disease.

Background: The diagnosis of Alzheimer's disease (AD) in its preclinical stages, such as subjective cognitive decline (SCD), is crucial for a timely management of the condition. However, current early diagnostic methods are unsuitable for preclinical screenings due to limited availability and diagnostic reliability. Additionally, reliance on invasive and scarcely available methods exacerbates the underdiagnosis of AD in its preclinical forms.

Multi-pathway blood biomarkers to target and monitor multidimensional prevention of cognitive and functional decline (nested in the IN-TeMPO study framed within the world-wide FINGERS network).

Background: As the population ages, the identification of preventive strategies able to delay cognitive and functional decline associated with aging represents a major challenge. To date, multidimensional approaches seem to be effective in reducing or delaying the onset of age-related diseases.

Objectives: The multicentric randomized controlled trial IN-TeMPO (ItaliaN study with Tailored Multidomain interventions to Prevent functional and cognitive decline in community-dwelling Older adults, ClinicalTrials.

stratified genome-wide association studies provide novel insights into the genetic etiology of Alzheimers's disease.

Among the more than 90 identified genetic risk loci for late-onset Alzheimer's disease (AD) and related dementias, the apolipoprotein E gene () ε2/ε3/ε4 polymorphism remains the longstanding benchmark for genetic disease risk with a consistently large effect across studies. Despite this massive signal, the exact mechanisms for how ε4 increases and for how ε2 decreases dementia risk is not well-understood. Importantly, recent trials of anti-amyloid therapies suggest less efficacy and higher risks of severe side effects in s4 carriers, hampering the treatment of those with the highest unmet need.

Genome-wide association studies of binge eating behaviour and anorexia nervosa yield insights into the unique and shared biology of eating disorder phenotypes.

Eating disorders -including anorexia nervosa (AN), bulimia nervosa, and binge eating disorder-are clinically distinct but exhibit symptom overlap and diagnostic crossover. Genomic analyses have mostly examined AN. We conducted the first genomic meta-analysis of binge eating behaviour (BE; 39,279 cases, 1,227,436 controls), alongside new analyses of AN (24,223 cases, 1,243,971 controls) and its subtypes (all European ancestries).

Evaluation of Illumina and Oxford Nanopore Sequencing for the Study of DNA Methylation in Alzheimer's Disease and Frontotemporal Dementia.

DNA methylation is a critical epigenetic mechanism involved in numerous physiological processes. Alterations in DNA methylation patterns are associated with various brain disorders, including dementias such as Alzheimer's disease (AD) and frontotemporal dementia (FTD). Investigating these alterations is essential for understanding the pathogenesis and progression of these disorders.

The two cut-offs approach for plasma p-tau217 in detecting Alzheimer's disease in subjective cognitive decline and mild cognitive impairment.

Background: The study aimed to explore the applicability of plasma phosphorylated tau (p-tau)217 in identifying patients with subjective cognitive decline (SCD) and mild cognitive impairment (MCI) carrying Alzheimer's disease (AD) pathology in real-world settings.

Methods: Fifty SCD, 87 MCI, and 50 AD-demented patients underwent blood collection to dose plasma p-tau217 with a fully automated Lumipulse G600II assay. Patients were classified according to the Revised Criteria of the Alzheimer's Association Workgroup as Core1+ or Core1- (based on amyloid positron emission tomography, cerebrospinal fluid [CSF] amyloid beta [Aβ]42/Aβ40, CSF p-tau181/Aβ42).

Fibrillar structures detected by AFM in the cerebrospinal fluid of patients affected by Alzheimer's disease and other neurological conditions.

Alzheimer's disease (AD) is a progressive debilitating neurodegenerative disorder that is usually diagnosed after irreversible brain damage has occurred. The detection and morphological characterization of amyloid-β fibrils, which are predominantly implicated in the pathogenic process of the disease, in the cerebrospinal fluid (CSF), emphasized the significance of examining such biofluid. In this work the crude CSF samples collected from patients with Alzheimer's disease and with other neurological conditions were analyzed by atomic force microscopy (AFM).

Towards a new Value-based scenario for the management of dementia in Italy: a SINdem delphi consensus study.

Unlabelled: This national expert-based Delphi-consensus aims at formulating recommendations on the management of dementia care in Italy. This effort seems important and timely given in light of a new scenario arising from a new biological definition of Alzheimer's disease (AD) and the availability of disease-modifying treatments (DMTs).

Methods: the Steering Committee of the Italian Neurological Society for dementia (SINdem) created appropriate statements.

Personalized brain models link cognitive decline progression to underlying synaptic and connectivity degeneration.

Cognitive decline is a condition affecting almost one sixth of the elder population and is widely regarded as one of the first manifestations of Alzheimer's disease. Despite the extensive body of knowledge on the condition, there is no clear consensus on the structural defects and neurodegeneration processes determining cognitive decline evolution. Here, we introduce a Brain Network Model (BNM) simulating the effects of neurodegeneration on neural activity during cognitive processing.

Targeting RPSA to modulate endosomal trafficking and amyloidogenesis in genetic Alzheimer's disease.

The "amyloid cascade hypothesis" for Alzheimer's disease (AD) pathogenesis, highlights the accumulation of amyloid-β (Aβ) as a crucial trigger for the pathology. However, AD is an extremely complex disease influenced by multiple pathophysiological processes, making it impossible to attribute its onset to a single hypothesis. The endocytic pathway, where the amyloidogenic processing of APP occurs, has emerged as a pathogenic "hub" for AD.

Open-label evaluation of oral trehalose in patients with neuronal ceroid lipofuscinoses.

The neuronal ceroid lipofuscinoses (NCLs) are incurable pediatric neurodegenerative diseases characterized by accumulation of lysosomal material and dysregulation of autophagy. Given the promising results of treatment with trehalose, an autophagy inducer, in cell and animal models of NCL, we conducted an open-label, non-placebo-controlled, non-randomized 12-month prospective study in NCL patients receiving oral trehalose (4 g/day). All were treated with a commercially available formulation for 6 months, followed by a 6-month washout.

Role of Blood P-Tau Isoforms (181, 217, 231) in Predicting Conversion from MCI to Dementia Due to Alzheimer's Disease: A Review and Meta-Analysis.

Blood-based biomarkers are minimally invasive tools to detect the pathological changes of Alzheimer's Disease (AD). This meta-analysis aims to investigate the use of blood-derived p-tau isoforms (181, 217, 231) to predict conversion from mild cognitive impairment (MCI) to AD dementia (ADD). Studies involving MCI patients with data on blood p-tau isoforms at baseline and clinical diagnosis at follow-up (≥1 year) were included.

Association between blood-based protein biomarkers and brain MRI in the Alzheimer's disease continuum: a systematic review.

Blood-based biomarkers (BBM) are becoming easily detectable tools to reveal pathological changes in Alzheimer's disease (AD). A comprehensive and up-to-date overview of the association between BBM and brain MRI parameters is not available. This systematic review aimed to summarize the literature on the associations between the main BBM and MRI markers across the clinical AD continuum.