Publications by authors named "Illan-Gala I"
Background: Neuroinflammation plays a major role in amyotrophic lateral sclerosis (ALS), and cumulative evidence suggests that systemic inflammation and the infiltration of immune cells into the brain contribute to this process. However, no study has investigated the role of peripheral blood immune cells in ALS pathophysiology using single-cell RNA sequencing (scRNAseq).
Methods: We aimed to characterize immune cells from blood and identify ALS-related immune alterations at single-cell resolution.
Frontotemporal dementia (FTD) is one of the leading causes of young-onset dementia before age 65, typically manifesting as abnormal behavior (in behavioral variant FTD) or language impairment (in primary progressive aphasia). Although FTD affects all populations across the globe, knowledge regarding the pathophysiology and genetics derives primarily from studies conducted in North America and Western Europe. Globally, biomedical research for FTD is hindered by variable access to diagnosis, discussed in this group's earlier article, and by reduced access to expertise, funding, and infrastructure.
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- A multicenter study involving 18 centers in 12 countries examined 360 patients with frontotemporal dementia (FTD) characterized by right anterior temporal lobe (RATL) atrophy to create a unified clinical description of the syndrome.
- Key symptoms identified in patients included mental rigidity (78%), disinhibition (74%), and naming difficulties (70%), with cognitive tests revealing specific deficits in social interactions and emotional recognition, though lacking in measuring mental rigidity.
- The findings represent the largest cohort of its kind, highlighting under-acknowledged symptoms of RATL and providing valuable insights for clinicians to improve early diagnosis and management of FTD patients.
Identification of a pathogenic mutation in in patients with amyotrophic lateral sclerosis.
J Neurol Neurosurg Psychiatry
January 2025
Background And Objective: Between 5% and 10% of amyotrophic lateral sclerosis (ALS) cases have a family history of the disease, 30% of which do not have an identifiable underlying genetic cause after a comprehensive study of the known ALS-related genes. Based on a significantly increased incidence of ALS in a small geographical region from Spain, the aim of this work was to identify novel ALS-related genes in ALS cases with negative genetic testing.
Methods: We detected an increased incidence of both sporadic and, especially, familial ALS cases in a small region from Spain compared with available demographic and epidemiological data.
Article Synopsis
- In frontotemporal lobar degeneration (FTLD), abnormal protein buildup in the brain correlates with declines in social-emotional and language skills, primarily involving TDP-43 or tau proteins.
- The study investigates how degeneration patterns in FTLD relate to gene expression of recently evolved genetic regions, using neuroimaging and transcriptomic data to examine targeted brain areas.
- Results indicate that FTLD subtypes uniquely or overlappingly affect brain regions tied to genes evolved in humans, with a notable relationship between TDP-43 function impairment and cryptic splicing in affected genes.
Article Synopsis
- Recent advances in blood markers for Alzheimer's disease detection show high accuracy, but their practicality in clinical settings remains uncertain due to the need for sensitive equipment.
- A study of 290 participants at a specialized memory clinic revealed that plasma pTau levels were significantly higher in those with amyloid-positive results compared to amyloid-negative individuals, indicating potential for blood tests in diagnosis.
- The automated platform demonstrated a strong capacity to accurately differentiate between amyloid-positive and amyloid-negative patients, with pTau showing the highest accuracy and a low misclassification rate, suggesting it could be a reliable diagnostic tool.
Minimally invasive biomarkers are urgently needed to detect molecular pathology in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Here, we show that plasma extracellular vesicles (EVs) contain quantifiable amounts of TDP-43 and full-length tau, which allow the quantification of 3-repeat (3R) and 4-repeat (4R) tau isoforms. Plasma EV TDP-43 levels and EV 3R/4R tau ratios were determined in a cohort of 704 patients, including 37 genetically and 31 neuropathologically proven cases.
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- * A study analyzed 4,685 sporadic FTD cases and found significant genetic variants at the MAPT and APOE loci that increase the risk for the disease, indicating potential genetic overlap with other neurodegenerative diseases.
- * The genetic risk factors appear to vary by population, with MAPT and APOE associations predominantly found in Central/Nordic and Mediterranean Europeans, suggesting a need for further research into these population-specific features for better understanding of sporadic FTD.
Article Synopsis
- Pathogenic heterozygous mutations in the GRN gene are a significant cause of frontotemporal dementia (FTD), leading to lower levels of the progranulin protein in biofluids, which has sparked therapeutic trials aimed at increasing these levels.
- A systematic review of literature on biofluid PGRN concentrations included data from 7071 individuals, primarily focusing on plasma PGRN levels derived from a single assay type, which accounted for variations based on mutation type, age, sex, and clinical diagnosis.
- Key findings established specific concentration cut-offs for plasma (74.8 ng/mL) and CSF (3.43 ng/mL) and indicated that plasma PGRN levels vary by mutation type,
Article Synopsis
- Amyotrophic lateral sclerosis (ALS) is a serious motor neuron disease that can also exhibit cognitive and behavioral symptoms, often overlapping with frontotemporal dementia (FTD) in some patients.
- * Around 50% of patients with motor neuron disease experience cognitive issues, with 10-15% meeting the criteria for FTD, emphasizing the need for better diagnostic tools.
- * A study analyzed data from 124 MND patients to understand the prevalence of FTD-related changes and identified specific clinical, genetic, and pathological subgroup characteristics, finding that 35.5% had features of frontotemporal lobar degeneration (FTLD).
Background: Recently developed blood markers for Alzheimer's disease (AD) detection have high accuracy but usually require ultra-sensitive analytic tools not commonly available in clinical laboratories, and their performance in clinical practice is unknown.
Methods: We analyzed plasma samples from 290 consecutive participants that underwent lumbar puncture in routine clinical practice in a specialized memory clinic (66 cognitively unimpaired, 130 participants with mild cognitive impairment, and 94 with dementia). Participants were classified as amyloid positive (A+) or negative (A-) according to CSF Aβ/Aβ ratio.
Article Synopsis
- The study investigates whether primary progressive apraxia of speech (PPAOS) and progressive agrammatic aphasia (PAA) are distinct conditions or part of a larger non-fluent aphasia spectrum.
- Using a group of 98 patients, the research examined speech and language characteristics, alongside disease severity, to identify meaningful clinical subgroups and potential shared pathologies.
- Findings indicated that most participants fit known clinical categories, but the overall data showed low clustering tendencies, suggesting that these speech disorders may not form clear, distinct syndromic entities.
Article Synopsis
- Frontotemporal lobar degeneration (FTLD) is a disease that affects how people think and communicate, causing issues in emotions and language.
- Researchers studied brain regions affected by FTLD to see if they are linked to special human genes that have changed through evolution.
- They found that certain genes related to brain functions are targeted by different types of FTLD, suggesting that this disease hits parts of the brain that have recently evolved to help humans.
Article Synopsis
- - The non-fluent/agrammatic variant of primary progressive aphasia (nfvPPA) is characterized by symptoms like apraxia of speech and expressive agrammatism, leading to varying speech-language difficulties among patients over time.
- - There is ongoing debate about whether to classify subtypes of nfvPPA based on symptom presence, including 'primary progressive apraxia of speech' and 'progressive agrammatic aphasia', but overlapping features challenge clear distinctions.
- - In a study involving 104 patients, researchers linked specific brain atrophy to varying speech-language symptoms, identifying that the neural correlates for both apraxia of speech and expressive agrammatism are located in the left posterior inferior frontal
Article Synopsis
- Frontotemporal dementia (FTD) is a major cause of dementia in people under 65, showing symptoms like unusual behavior or language difficulties depending on the variant.
- The symptoms and presentation of FTD can differ significantly across cultures and socioeconomic backgrounds, but most current research is based on Western populations.
- The paper discusses how global diversity influences FTD's diagnosis and treatment, and suggests changes to improve the understanding and management of FTD worldwide.
Background: Primary progressive aphasia (PPA) is a group of neurodegenerative disorders including Alzheimer's disease and frontotemporal dementia characterized by language deterioration. Transcranial direct current stimulation (tDCS) is a non-invasive intervention for brain dysfunction.
Objective: To evaluate the tolerability and efficacy of tDCS combined with speech therapy in the three variants of PPA.
The study of sex differences in Alzheimer's disease is increasingly recognized as a key priority in research and clinical development. People with Down syndrome represent the largest population with a genetic link to Alzheimer's disease (>90% in the 7th decade). Yet, sex differences in Alzheimer's disease manifestations have not been fully investigated in these individuals, who are key candidates for preventive clinical trials.
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- The study investigates the relationship between visual artistic creativity (VAC) and frontotemporal dementia (FTD), suggesting that VAC can emerge early in FTD and may be linked to changes in the dorsomedial occipital cortex.
- A total of 689 FTD patients were analyzed, with 17 showing VAC, and their data were compared with two control groups to understand the neuroanatomical and physiological basis of VAC in FTD.
- Results highlighted that VAC often coincides with the onset of FTD symptoms and is associated with specific brain atrophy patterns, particularly in the dorsomedial occipital region, which may play a role in visual creative processes.
Neuroinflammation-Related Proteins NOD2 and Spp1 Are Abnormally Upregulated in Amyotrophic Lateral Sclerosis.
Neurol Neuroimmunol Neuroinflamm
March 2023
Background And Objectives: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of unknown etiology and poorly understood pathophysiology. There is no specific biomarker either for diagnosis or prognosis. The aim of our study was to investigate differentially expressed proteins in the CSF and serum from patients with ALS to determine their role in the disease process and evaluate their utility as diagnostic or prognostic biomarkers.
View Article and Find Full Text PDFThe most frequent genetic cause of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) is the hexanucleotide repeat expansion in C9orf72. An important neuropathological hallmark associated with this mutation is the accumulation of the phosphorylated form of TAR (trans-activation response element) DNA-binding protein 43 (pTDP-43). Glia plays a crucial role in the neurodegeneration observed in C9orf72-associated disorders.
View Article and Find Full Text PDFThe progressive supranuclear palsy (PSP) syndrome encompasses different entities. PSP disease of sporadic origin is the most frequent presentation, but different genetic mutations can lead either to monogenic variants of PSP disease, or to other conditions with a different pathophysiology that eventually may result in PSP phenotype. PSP syndrome of monogenic origin is poorly understood due to the low prevalence and variable expressivity of some mutations.
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