Recent research reveals an overlap between frontotemporal dementia (FTD) and a variety of primary psychiatric disorders, challenging the artificial divisions between psychiatry and neurology. This chapter offers an overview of the clinical syndromes associated with FTD while describing links between these syndromes and neuroimaging. This is followed by a review of the neuropathology and genetic changes in the brain. We will illustrate the syndromic overlap that exists between FTD and several primary psychiatric disorders including bipolar affective disorder and schizophrenia. Emphasis will be placed on the behavioral variant of FTD (bvFTD), which is the common clinical syndrome seen with degeneration of the frontal lobes and is the most likely to be encountered in psychiatric settings.
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http://dx.doi.org/10.1016/B978-0-444-64012-3.00003-4 | DOI Listing |
J Neuropathol Exp Neurol
January 2025
Department of Biological Sciences, Delaware State University, Dover, DE, United States.
Trans-active response DNA-binding protein-43 (TDP-43) is the major pathological protein in motor neuron disease and TDP-43 pathology has been described in the brains of up to 50% of patients with Alzheimer disease (AD). Hippocampal sclerosis of aging (HS-A), an age-related neuropathology characterized by severe neuronal loss and gliosis in CA1 and/or subiculum, is found in ∼80% of cases that are positive for phosphorylated TDP-43. HS-A is seen as a co-pathology in cases with AD, limbic-predominant age-related TDP-43 encephalopathy neuropathologic changes (LATE-NC), and frontotemporal degeneration.
View Article and Find Full Text PDFLancet Neurol
February 2025
Brain and Mind Centre, The University of Sydney, Sydney, NSW 2050, Australia; Department of Neurology, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
Lancet Neurol
February 2025
Department of Neurosciences, and Leuven Brain Institute, University of Leuven, Leuven, Belgium; Laboratory of Neurobiology, Center for Brain & Disease Research, VIB, Leuven, Belgium. Electronic address:
Autosomal dominant mutations in the gene encoding the DNA and RNA binding protein FUS are a cause of amyotrophic lateral sclerosis (ALS), and about 0·3-0·9% of patients with ALS are FUS mutation carriers. FUS-mutation-associated ALS (FUS-ALS) is characterised by early onset and rapid progression, compared with other forms of ALS. However, different pathogenic mutations in FUS can result in markedly different age at symptom onset and rate of disease progression.
View Article and Find Full Text PDFLancet Neurol
February 2025
Department of Clinical Neurological Sciences, University of Western Ontario, London, ON, Canada; Department of Cognitive Neurology, St Joseph's Health Care London, London, ON, Canada. Electronic address:
Background: No treatments exist for apathy in people with frontotemporal dementia. Previously, in a randomised double-blind, placebo-controlled, dose-finding study, intranasal oxytocin administration in people with frontotemporal dementia improved apathy ratings on the Neuropsychiatric Inventory over 1 week and, in a randomised, double-blind, placebo-controlled, crossover study, a single dose of 72 IU oxytocin increased blood-oxygen-level-dependent signal in limbic brain regions. We aimed to determine whether longer treatment with oxytocin improves apathy in people with frontotemporal dementia.
View Article and Find Full Text PDFJ Fungi (Basel)
January 2025
Department of Chemistry and Biochemistry, Brooklyn College, Brooklyn, NY 11210, USA.
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are incurable neurodegenerative disorders sharing pathological and genetic features, including mutations in the gene. FUS is an RNA-binding protein that mislocalizes to the cytoplasm and aggregates in ALS/FTD. In a yeast model, FUS proteinopathy is connected to changes in the epigenome, including reductions in the levels of H3S10ph, H3K14ac, and H3K56ac.
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