Researchers from many Catalan hospitals and research facilities have revealed links between frontotemporal dementia and amyotrophic lateral sclerosis (ALS), two debilitating brain disorders, in a study that was published in the journal Brain.
The study explores the relationship and spectrum of these two neurodegenerative diseases, which have more in common than previously believed. It is led by Drs. Álvaro Carbayo and Ricard Rojas of the Sant Pau Research Institute’s Neuromuscular Diseases Group and is conducted in collaboration with Drs. Sergi Borrego-Écija and Ellen Gelpi of the Alzheimer’s Disease and Other Cognitive Disorders Group and the Neurological Tissue Bank of IDIBAPS.
Dr. Ricard Rojas, head of the Neurodegenerative Diseases Unit at the Neurology Service of Sant Pau Hospital and researcher at IR Sant Pau, explained that both frontotemporal dementia, which is characterized by cognitive and behavioral problems, and ALS share a common but highly heterogeneous clinical, genetic, and pathological spectrum. ALS affects motor neurons.
According to clinical research, up to 50% of ALS patients may experience behavioral and cognitive symptoms; of these, 10 to 15% particularly fit the frontotemporal dementia diagnostic criteria.
In a recent neuropathological analysis of a sizable number of ALS cases, the true number may be significantly higher: Additionally, frontotemporal dementia pathological characteristics were found in 35.5% of patients.Results indicate that 93.6% of ALS cases had abnormal TDP-43 protein aggregation, which was particularly widespread in cases where frontotemporal dementia pathology coexisted.
Although TDP-43 protein aggregates are known to be present in most cases, the study emphasizes the notable variability of neuropathological features, pointing to potential differences in pathophysiological causes. It is significant to highlight that, in the lack of an accurate biomarker, the identification of these proteins is currently done post-mortem.
“Neuropathological studies and correlation with clinical characteristics help us expand our knowledge of the basis of diseases such as ALS and frontotemporal dementia, opening doors to future studies on biomarkers and specific therapies,” says Dr. Carbayo, the primary author of the study.
Regardless of their final clinical diagnosis, all cases from the Neurological Tissue Bank of the FRCB-IDIBAPS-Clinic Hospital of Barcelona between 1994 and 2022 that satisfied the neuropathological criteria for frontotemporal dementia were included in the study.
Through a retrospective evaluation of clinical and neuropathological data, key clinical, genetic, and pathogenic features may be analyzed. Patient groups with and without frontotemporal dementia pathology abnormalities could be compared to identify distinct subgroups.
“We have observed astonishing heterogeneity in the clinical presentation and pathological and genetic characteristics of patients, with a higher frequency of frontotemporal dementia than described in other series,” according to Dr. Carbayo.
According to him, these findings highlight the value of multidisciplinary cooperation between frontotemporal dementia and ALS experts and departments.
To provide our patients with better care and a deeper understanding of the range of neurodegenerative illnesses, collaboration is essential. We have been utilizing this construction at Sant Pau for the past six or seven years,” Dr. Carbayo says.
Journal Reference
Álvaro Carbayo et al, Clinicopathological correlates in frontotemporal lobar degeneration: motor neuron disease spectrum, Brain (2024). DOI: 10.1093/brain/awae011.
