Frontotemporal dementia (FTD) is the second most common form of young-onset (<65 years) dementia. Clinically, it primarily manifests as a disorder of behavioural, executive, and/or language functions. Pathologically, frontotemporal lobar degenerat...
Frontotemporal lobar degeneration (FTLD) includes a heterogeneous group of disorders pathologically characterized by the degeneration of the frontal and temporal lobes. In addition to major genetic contributors of FTLD such as mutations in MAPT, GRN,...
Frontotemporal lobar degeneration (FTLD) is a neurodegenerative disorder clinically characterized by behavioral, language, and motor symptoms, with major impact on the lives of patients and their families. TDP-43 proteinopathy is the underlying neuro...
Emerging data suggest the roles of endo-lysosomal dysfunctions in frontotemporal lobar degeneration (FTLD) and in other dementias. Cathepsin D is one of the major lysosomal proteases, mediating the degradation of unfolded protein aggregates. In this...
Cutting-edge research suggests endosomal/immune dysregulation in GRN/C9orf72-associated frontotemporal lobar degeneration (FTLD). In this retrospective study, we investigated plasma small extracellular vesicles (sEVs) and complement proteins in 172 s...
Genetic frontotemporal lobar degeneration (FTLD) is characterized by heterogeneous phenotypic expression, with a disease onset highly variable even in patients carrying the same mutation. Herein we investigated if variants in lysosomal genes modulate...
Alzheimer’s disease (AD) and Frontotemporal lobar degeneration (FTLD) represent the most common forms of neurodegenerative dementias with a highly phenotypic variability. Herein, we investigated the role of genetic variants related to the immun...
Neuropsychological tests (NPTs), which are routinely used in clinical practice for assessment of dementia, are also considered to be essential for differential diagnosis of Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD),...
Accurately diagnosing Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD) is challenging due to overlapping symptoms and limitations of current imaging methods. This study investigates the use of [11C]PBB3 PET/CT imaging to vi...
Transactivation response DNA binding protein 43 kDa (TDP-43) is known to be a pathologic protein in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). TDP-43 is normally a nuclear protein, but affected neurons of ALS or...
Loss-of-function (LOF) mutations in GRN gene, which encodes progranulin (PGRN), cause frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP). FTLD-TDP is one of the most common forms of early onset dementia, but its pathogenesis is not f...
Recently, disease-associated variants of the TUBA4A gene were identified in patients with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here, we present the neuropathological report of a patient with the semantic variant of p...
Frontotemporal lobar degeneration (FTLD) belongs to a heterogeneous group of highly complex neurodegenerative diseases and represents the second cause of presenile dementia in individuals under 65. Frontotemporal-TDP is a subgroup of frontotemporal d...
Abnormal cytoplasmic aggregates containing the TDP-43 protein and its fragments are present in the central nervous system of the majority of patients with amyotrophic lateral sclerosis (ALS) and in patients with frontotemporal lobar degeneration (FTL...
Parkin and PINK1 are key regulators of mitophagy, an autophagic pathway for selective elimination of dysfunctional mitochondria. To this date, parkin depletion has been associated with recessive early onset Parkinson’s disease (PD) caused by lo...
Background: Patients with a frontotemporal lobar degeneration (FTLD) usually manifest with behavioral variant frontotemporal dementia (bvFTD). Alzheimer’s disease (AD) may also manifest with a predominant behavioral-dysexecutive syndrome, simil...
Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are neurodegenerative disorders that exist on a disease spectrum due to pathological, clinical and genetic overlap. In up to 97% of ALS cases and ~50% of FTLD cases, the...
Mutations in granulin (GRN) have been associated with neurodegenerative diseases, such as frontotemporal lobar degeneration (FTLD) and neuronal ceroid lipofuscinosis (NCL). In Portugal, GRN mutations account for around half of all FTLD cases with kno...
Despite Artificial Intelligence (AI) being a leading technology in biomedical research, real-life implementation of AI-based Computer-Aided Diagnosis (CAD) tools into the clinical setting is still remote due to unstandardized practices during develop...
Neurodegenerative diseases such as Alzheimer’s disease (AD), frontotemporal lobar degeneration (FTLD), and α-synucleinopathies—including Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (M...
Recent findings of diverse populations of prion-like conformers of misfolded tau protein expand the prion concept to Alzheimer’s disease (AD) and monogenic frontotemporal lobar degeneration (FTLD)-MAPT P301L, and suggest that distinct strains o...
Transactive response DNA-binding protein of 43 kDa (TDP-43) and tau proteins play critical roles in neurodegenerative diseases, particularly frontotemporal lobar degeneration (FTLD) and Alzheimer’s disease (AD). The co-occurrence of TDP-43 and...
Dementia is broadly characterized by cognitive and psychological dysfunction that significantly impairs daily functioning. Dementia has many causes including Alzheimer’s disease (AD), dementia with Lewy bodies (DLB), and frontotemporal lobar degenera...
Frontotemporal lobar degeneration (FTLD) is a complex disease, characterized by progressive degeneration of frontal and temporal lobes. Mutations in progranulin (GRN) gene have been found in up to 50% of patients with familial FTLD. Abnormal deposits...
Dysfunctions in the endo-lysosomal system have been hypothesized to underlie neurodegeneration in major neurocognitive disorders due to Alzheimer’s disease (AD), Frontotemporal Lobar Degeneration (FTLD), and Lewy body disease (DLB). The aim of...
Background and Objective: Primary Progressive Aphasias (PPAs) are rare neurodegenerative disorders classified within frontotemporal lobar degeneration (FTLD) and typically manifest between 45 and 70 years of age. In Mexico—and many other countr...
Amyotrophic lateral sclerosis (ALS) is a devastating, uniformly lethal progressive degenerative disorder of motor neurons that overlaps with frontotemporal lobar degeneration (FTLD) clinically, morphologically, and genetically. Although many distinct...
Slow-onset neurodegenerative disease in a low-expresser 2N4R P301L transgenic (Tg) mouse model is marked by neuroinflammation and by differing patterns of CNS deposition and accumulation of tau conformers, with such heterogeneities present even withi...
Despite an early understanding of amyotrophic lateral sclerosis (ALS) as a disease affecting the motor system, including motoneurons in the motor cortex, brainstem, and spinal cord, today, many cases involving dementia and behavioral disorders are re...
Functional near-infrared spectroscopy (fNIRS) is an innovative neuroimaging method that offers several advantages over other commonly used modalities. This narrative review investigated the potential contribution of this method to the study of neurod...
We analysed the expression levels of 84 key genes involved in the regulated degradation of cellular protein by the ubiquitin-proteasome system in peripheral cells from patients with frontotemporal dementia (FTD) due to C9ORF72 and GRN mutations, as c...
Amyotrophic lateral sclerosis (ALS) has long been considered to be a purely motor disorder. However, it has become apparent that many ALS patients develop cognitive and behavioral manifestations similar to frontotemporal dementia and the term amyotro...
Tauopathies represent a vast family of neurodegenerative diseases, the most well-known of which is Alzheimer’s disease. The symptoms observed in patients include cognitive deficits and locomotor problems and can lead ultimately to dementia. The commo...
The transmembrane protein 106B (TMEM106B) gene is a susceptibility factor and disease modifier of frontotemporal dementia, but few studies have investigated its role in amyotrophic lateral sclerosis. The aim of this work was to assess the impact of t...
The cell-to-cell transmission of tau aggregates is considered a mechanism underlying the intracerebral spreading of tau pathology in Alzheimer’s disease (AD) and other tauopathies. Recent studies suggest that tau oligomers, rather than fibrils,...
Extracellular vesicles (EVs) play a central role in neurodegenerative diseases (NDs) since they may either spread the pathology or contribute to the intracellular protein quality control (PQC) system for the cellular clearance of NDs-associated prote...
Billions of people are exposed to fine particulate matter (PM2.5) levels above the USEPA’s annual standard of 9 μg/m3. Common emission sources are anthropogenic, producing complex aerosolized toxins. Ultrafine particulate matter (UFPM) and i...
The abnormal deposition of pathogenic forms of tau protein in the brain is a main feature and a major determinant of cognitive decline in many neurodegenerative disorders including Alzheimer’s disease and frontotemporal lobar degeneration [...]
Polymorphisms in certain inflammatory-related genes have been identified as putative differential risk factors of neurodegenerative diseases with abnormal protein aggregates, such as sporadic Alzheimer’s disease (AD) and sporadic Parkinson’s disease...
The behavioral variant of frontotemporal dementia (bvFTD) is a clinical syndrome resulting from various causes of neuronal demises associated with frontotemporal lobar degeneration. Symptoms include behavioral and personality changes, social cognitiv...
The identification of TDP-43 as the major component of the pathologic inclusions in most forms of sporadic and familial frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U) and amyotrophic lateral sclerosis (ALS) resolved a l...
Frontotemporal lobar degeneration, the neuropathological substrate of frontotemporal dementia (FTD), is characterized by the deposition of protein aggregates, including tau. Evidence has shown concomitant amyloid pathology in some of these patients,...
Fused in sarcoma (FUS) is a DNA/RNA binding protein that is involved in RNA metabolism and DNA repair. Numerous reports have demonstrated by pathological and genetic analysis that FUS is associated with a variety of neurodegenerative diseases, includ...
TAR DNA binding protein 43 (TDP-43) is a DNA/RNA binding protein involved in pivotal cellular functions, especially in RNA metabolism. Hyperphosphorylated and ubiquitinated TDP-43-positive neuronal cytoplasmic inclusions are identified in the brain a...
Frontotemporal lobar degeneration (FTLD) represents a heterogeneous group of neurodegenerative disorders with overlapping clinical, pathological, and genetic characteristics. Increasing evidence indicates that disease mechanisms begin decades before...
(1) Background: Frontotemporal lobar degeneration (FTLD) is a generic term which refers to multiple pathologies, including FTLD-tau. The most common FTLD-tau diseases are Pick’s disease (PiD), progressive supranuclear palsy (PSP) and corticobas...
Neurodegeneration elicits neuroinflammatory responses to kill pathogens, clear debris and support tissue repair. Neuroinflammation is a dynamic biological response characterized by the recruitment of innate and adaptive immune system cells in the sit...
Transactive response DNA-binding protein 43 (TDP-43) is a nucleic acid-binding protein that is involved in transcription and translation regulation, non-coding RNA processing, and stress granule assembly. Aside from its multiple functions, it is also...
To date, no neurodegenerative diseases (NDDs) have cures, and the underlying mechanism of their pathogenesis is undetermined. As miRNAs extensively regulate all biological processes and are crucial regulators of healthy brain function, miRNAs differe...
DNA damage causes PARP1 activation in the nucleus to set up the machinery responsible for the DNA damage response. Here, we report that, in contrast to cytoplasmic PARPs, the synthesis of poly(ADP-ribose) by PARP1 opposes the formation of cytoplasmic...
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