Targeted long-read sequencing to quantify methylation of the C9orf72 repeat expansion.

Background: The gene C9orf72 harbors a non-coding hexanucleotide repeat expansion known to cause amyotrophic lateral sclerosis and frontotemporal dementia. While previous studies have estimated the length of this repeat expansion in multiple tissues, technological limitations have impeded researchers from exploring additional features, such as methylation levels.

Methods: We aimed to characterize C9orf72 repeat expansions using a targeted, amplification-free long-read sequencing method.

Time-Frequency functional connectivity alterations in Alzheimer's disease and frontotemporal dementia: An EEG analysis using machine learning.

Objective: Alzheimer's disease (AD) and frontotemporal dementia (FTD) are prevalent neurodegenerative diseases characterized by altered brain functional connectivity (FC), affecting over 100 million people worldwide. This study aims to identify distinct FC patterns as potential biomarkers for differential diagnosis.

Methods: Resting-state EEG data from 36 AD patients, 23 FTD patients, and 29 healthy controls were analyzed using time-frequency and bandpass filtering FC metrics.

WDR49-Positive Astrocytes Mark Severity of Neurodegeneration in Frontotemporal Lobar Degeneration and Alzheimer's Disease.

A subpopulation of astrocytes expressing WD Repeat Domain 49 (WDR49) was recently identified in frontotemporal lobar degeneration (FTLD) with GRN pathogenic variants. This is the first study to investigate their expression and relation to pathology in other FTLD subtypes and Alzheimer's disease (AD). In a postmortem cohort of TDP-43 proteinopathies (12 GRN, 11 C9orf72, 9 sporadic TDP-43), tauopathies (13 MAPT, 8 sporadic tau), 10 AD, and four controls, immunohistochemistry and immunofluorescence were performed for WDR49 and pathological inclusions on frontal, temporal, and occipital cortical sections.

The Turkish validity and reliability of Addenbrooke's Cognitive Examination III.

Background: Addenbrooke's Cognitive Examination III (ACE-III) was developed as a screening tool for cognitive disorders. Many countries have proven the cultural adaptation, reliability and validity of ACE-III.

Aims: To make cultural adaptations of ACE-III for the Turkish population and to examine its validity and reliability.

Plasma extracellular vesicle: a novel biomarker for neurodegenerative disease diagnosis.

Extracellular vesicles (EVs) are membrane-bound structures that carry proteins, lipids, RNA, and DNA, playing key roles in cell communication and material transport. Recent research highlights their potential as disease biomarkers due to their stability in bodily fluids. This study explores using tau and TDP-43 proteins in plasma EVs as diagnostic biomarkers for frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS).

Greater baseline cortical atrophy in the dorsal attention network predicts faster clinical decline in Posterior Cortical Atrophy.

Background: Posterior Cortical Atrophy (PCA) is a clinical syndrome characterized by progressive visuospatial and visuoperceptual impairment. As the neurodegenerative disease progresses, patients lose independent functioning due to the worsening of initial symptoms and development of symptoms in other cognitive domains. The timeline of clinical progression is variable across patients, and the field currently lacks robust methods for prognostication.

Rivastigmine interferes with the pharmacological activity of hydromethylthionine on presynaptic proteins in the line 66 model of frontotemporal dementia.

The negative interference of treatments between the acetylcholinesterase inhibitor rivastigmine and the tau aggregation inhibitor hydromethylthionine mesylate (HMTM) has been reported in Line 1 tau-transgenic mice, which overexpress a truncated species of tau protein that is found in the core of paired helical filaments in Alzheimer´s disease (AD). However, little is known about whether such interactions could affect synapses in mice overexpressing tau carrying pathogenic mutations. Here, we have used Line 66 (L66) mice which overexpress full-length human tau carrying the P301S mutation as a model in which tau accumulates in synapses.

Pyridazine Compounds as NLRP3 Inhibitors for Treating Parkinson's Disease or Frontotemporal Dementia.

Provided herein are novel pyridazine compounds as NLRP3 inhibitors, pharmaceutical compositions, use of such compounds in treating Parkinson's disease or frontotemporal dementia, and processes for preparing such compounds.

Examining the potential involvement of NONO in TDP-43 proteinopathy in Drosophila.

The misfolding and aggregation of TAR DNA binding protein-43 (TDP-43), leading to the formation of cytoplasmic inclusions, emerge as a key pathological feature in a spectrum of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar dementia (FTLD). TDP-43 shuttles between the nucleus and cytoplasm but forms nuclear bodies (NBs) in response to stress. These NBs partially colocalise with nuclear speckles and paraspeckles that sequester RNAs and proteins, thereby regulating many cellular functions.

Statistical examination of shared loci in neuropsychiatric diseases using genome-wide association study summary statistics.

Continued methodological advances have enabled numerous statistical approaches for the analysis of summary statistics from genome-wide association studies. Genetic correlation analysis within specific regions enables a new strategy for identifying pleiotropy. Genomic regions with significant 'local' genetic correlations can be investigated further using state-of-the-art methodologies for statistical fine-mapping and variant colocalisation.

18F-FDG metabolic abnormalities precede perfusion and atrophic changes in diagnosis of early frontotemporal dementia: study from a tertiary care university hospital.

Objective: Diagnosis of early onset dementia is critical for initiating management. Although structural MRI is an established procedure for dementia evaluation, early cases may be missed. Neurodegenerative diseases lead to reductions in glucose consumption and grey matter volume loss.

The Underestimated Role of Iron in Frontotemporal Dementia: A Narrative Review.

The term frontotemporal dementia (FTD) comprises a group of neurodegenerative disorders characterized by the progressive degeneration of the frontal and temporal lobes of the brain with language impairment and changes in cognitive, behavioral and executive functions, and in some cases motor manifestations. A high proportion of FTD cases are due to genetic mutations and inherited in an autosomal-dominant manner with variable penetrance depending on the implicated gene. Iron is a crucial microelement that is involved in several cellular essential functions in the whole body and plays additional specialized roles in the central nervous system (CNS) mainly through its redox-cycling properties.

Use of Artificial Intelligence in Imaging Dementia.

Alzheimer's disease is the most common cause of dementia in the elderly population (aged 65 years and over), followed by vascular dementia, Lewy body dementia, and rare types of neurodegenerative diseases, including frontotemporal dementia. There is an unmet need to improve diagnosis and prognosis for patients with dementia, as cycles of misdiagnosis and diagnostic delays are challenging scenarios in neurodegenerative diseases. Neuroimaging is routinely used in clinical practice to support the diagnosis of neurodegenerative diseases.

Two novel variants in GRN: the relevance of CNV analysis and genetic screening in FTLD patients with a negative family history.

Background: Frontotemporal lobar degeneration (FTLD) is one of the leading causes of early onset dementia. Pathogenic variants in GRN have been reported to cause 5-25% of familial and 5% of sporadic FTLD. Here, we present two novel, likely pathogenic variants in GRN.

Musicality and social cognition in dementia: clinical and anatomical associations.

Human musicality might have co-evolved with social cognition abilities, but common neuroanatomical substrates remain largely unclear. In behavioural variant frontotemporal dementia, social cognitive abilities are profoundly impaired, whereas these are typically spared in Alzheimer's disease. If musicality indeed shares a neuroanatomical basis with social cognition, it could be hypothesized that clinical and neuroanatomical associations of musicality and social cognition should differ between these causes of dementia.

Mild cognitive impairment in spontaneous intracranial hypotension and its rapid reversal by repair of a spinal cerebrospinal fluid leak.

Background: Patients with spontaneous intracranial hypotension (SIH) report difficulties in concentration and memory. To objectify these deficits, we implemented standard cognitive tests into our routine SIH workup.

Method: Retrospective, single-center report of cognitive standard tests among patients with SIH consecutively admitted from May to July 2023.

Skull defect - Frontotemporal dementia sagging brain syndrome.

Objective: Frontotemporal dementia (FTD) sagging brain syndrome is a disabling condition. An underlying spinal Cerebrospinal fluid leak can be identified in only a minority of patients and the success rate of non-directed treatments is low. Some of these patients have a remote history of craniectomy/cranioplasty and we report a positive response to custom implant cranioplasty revision many years after their initial cranioplasty.

Targeting tau in Alzheimer's and beyond: Insights into pathology and therapeutic strategies.

Tauopathies encompass a group of approximately 20 neurodegenerative diseases characterized by the accumulation of the microtubule-associated protein tau in brain neurons. The pathogenesis of intracellular neurofibrillary tangles, a hallmark of tauopathies, is initiated by hyperphosphorylated tau protein isoforms that cause neuronal death and lead to diseases like Alzheimer's, Parkinson's disease, frontotemporal dementia, and other complex neurodegenerative diseases. Current applications of tau biomarkers, including imaging, cerebrospinal fluid, and blood-based assays, assist in the evaluation and diagnosis of tauopathies.

Actigraphy validation in behavioral variant frontotemporal dementia.

Background: Actigraphy is increasingly being used to assess sleep in patients with neurodegenerative diseases. However, information on its accuracy relative to polysomnography (PSG) in this clinical population remains scarce. This study investigates the performance of actigraphy compared to PSG in patients with behavioral variant frontotemporal dementia (bvFTD), which is the leading form of early-onset dementia.

Semantic behavioral variant frontotemporal dementia and semantic dementia associated with mutations.

Frontotemporal dementia (FTD) is a highly heritable group of neurodegenerative disorders, characterized by varying clinical and pathological features. gene has been described worldwide within the FTD/ALS spectrum but its association with right and left temporal variant of FTD (tvFTD) is still unclear. This study aimed to reclassify a Sardinian FTD cohort according to proposed criteria for the semantic behavioral variant FTD (sbvFTD), explore mutations' association with tvFTD, and review related literature.

Unraveling the molecular basis for G-quadruplex-binders to ALS/FTD-associated G4C2 repeats of the C9orf72 gene.

The most recurrent familial cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is the presence of an abnormal number of intronic GGGGCC (G4C2) repetitions in the C9orf72 gene, which has been proposed to drive ALS/FTD pathogenesis. Recently, it has been shown that such G4C2 repetitions can fold into G-quadruplex (G4) secondary structures. These G4s have been selectively stabilized by small-molecule binders, furnishing proof of principle that targeting these non-canonical nucleic acid sequences represents a novel and effective therapeutic strategy to tackle neurodegenerative disorders.

repeat expansion creates the unstable folate-sensitive fragile site FRA9A.

The hyper-unstable Chr9p21 locus, harbouring the interferon gene cluster, oncogenes and , is linked to multiple diseases. (GGGGCC)n expansions (Exp) are associated with incompletely penetrant amyotrophic lateral sclerosis, frontotemporal dementia and autoimmune disorders. Exp patients display hyperactive cGAS-STING-linked interferon immune and DNA damage responses, but the source of immunostimulatory or damaged DNA is unknown.