Background: Frontotemporal lobar degeneration (FTLD) is a neuropathological construct with multiple clinical presentations, including the behavioural variant of frontotemporal dementia (bvFTD), primary progressive aphasia-both non-fluent variant (nfvPPA) and semantic variant (svPPA)-progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), characterised by the deposition of abnormal tau protein in the brain. A major challenge for treating FTLD is early diagnosis and accurate discrimination among different syndromes. The main goal here was to investigate the cortical architecture of FTLD syndromes using cortical diffusion tensor imaging (DTI) analysis and to test its power to discriminate between different clinical presentations.
Methods: A total of 271 individuals were included in the study: 87 healthy subjects (HS), 31 semantic variant primary progressive aphasia (svPPA), 37 behavioural variant (bvFTD), 30 non-fluent/agrammatic variant primary progressive aphasia (nfvPPA), 47 PSP Richardson's syndrome (PSP-RS) and 39 CBS cases. 3T MRI T1-weighted images and DTI scans were analysed to extract three cortical DTI derived measures (AngleR, PerpPD and ParlPD) and mean diffusivity (MD), as well as standard volumetric measurements. Whole brain and regional data were extracted. Linear discriminant analysis was used to assess the group discrimination capability of volumetric and DTI measures to differentiate the FTLD syndromes. In addition, in order to further investigate differential diagnosis in CBS and PSP-RS, a subgroup of subjects with autopsy confirmation in the training cohort was used to select features which were then tested in the test cohort. Three different challenges were explored: a binary classification (controls vs all patients), a multiclass classification (HS vs bvFTD vs svPPA vs nfvPPA vs CBS vs PSP-RS) and an additional binary classification to differentiate CBS and PSP-RS using features selected in an autopsy confirmed subcohort.
Results: Linear discriminant analysis revealed that PerpPD was the best feature to distinguish between controls and all patients (ACC 86%). PerpPD regional values were able to classify correctly the different FTLD syndromes with an accuracy of 85.6%. The PerpPD and volumetric values selected to differentiate CBS and PSP-RS patients showed a classification accuracy of 85.2%.
Conclusions: (I) PerpPD achieved the highest classification power for differentiating healthy controls and FTLD syndromes and FTLD syndromes among themselves. (II) PerpPD regional values could provide an additional marker to differentiate FTD, PSP-RS and CBS.
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http://dx.doi.org/10.1186/s13195-021-00914-4 | DOI Listing |
Mov Disord
January 2025
Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
Background: Perry syndrome (PS) is a rare and fatal hereditary autosomal dominant neurodegenerative disorder caused by mutations in dynactin (DCTN1). PS brains accumulate inclusions positive for ubiquitin, transactive-response DNA-binding protein of 43 kDa (TDP-43), and to a lesser extent dynactin.
Objectives: Little is known regarding the contributions of TDP-43, an RNA binding protein that represses cryptic exon inclusion, in PS.
Trends Genet
January 2025
Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Hessen, 61231, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Bad Nauheim, Hessen, 61231, Germany; Excellence Cluster Cardio-Pulmonary Institute (CPI), Bad Nauheim, Frankfurt, Giessen, Germany. Electronic address:
The onset and progression of dominant diseases are thought to result from haploinsufficiency or dominant negative effects. Here, we propose transcriptional adaptation (TA), a newly identified response to mRNA decay, as an additional cause of some dominant diseases. TA modulates the expression of so-called adapting genes, likely via mRNA decay products, resulting in genetic compensation or a worsening of the phenotype.
View Article and Find Full Text PDFAlzheimers Dement
January 2025
Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
Introduction: Plasma-based biomarkers have shown promise for clinical implementation, but their accuracy in differentiating Alzheimer's disease (AD) from syndromes associated with frontotemporal lobar degeneration (FTLD) has yet to be fully investigated. This study assessed the potential of plasma biomarkers for differential diagnosis.
Methods: This cohort study included 374 participants (96 AD, 278 FTLD).
Neurol Sci
January 2025
Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milano, Italy.
Background: This study aimed to assess the screening properties of Foderaro et al.s' updated normative framework for the Italian MMSE in detecting mild cognitive impairment (MCI) and dementia due to neurodegenerative, chronic cerebrovascular, and mixed etiologies, as well as in differentiating between these two syndromes.
Methods: Data on 234 patients with either MCI (N = 83) or dementia (N = 151) due to Alzheimer's disease (N = 112), Lewy body disease (N = 11), frontotemporal lobar degeneration (N = 20), chronic cerebrovascular disease (N = 39), or mixed (N = 47) etiologies having been administered Foderaro et al.
Sci Rep
January 2025
Department of Protein Science, SciLifeLab, KTH Royal Institute of Technology, Stockholm, Sweden.
Accurate diagnosis and monitoring of neurodegenerative diseases require reliable biomarkers. Cerebrospinal fluid (CSF) proteins are promising candidates for reflecting brain pathology; however, their diagnostic utility may be compromised by natural variability between individuals, weakening their association with disease. Here, we measured the levels of 69 pre-selected proteins in cerebrospinal fluid using antibody-based suspension bead array technology in a multi-disease cohort of 499 individuals with neurodegenerative disorders including Alzheimer's disease (AD), behavioral variant frontotemporal dementia, primary progressive aphasias, amyotrophic lateral sclerosis (ALS), corticobasal syndrome, primary supranuclear palsy, along with healthy controls.
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