Enligt a recent study published in the research journal Brain, brain pathology consistent with FTD was detected in roughly 35% of the participants with motor neuron disease, which includes diseases like ALS. Abnormal protein clumps were detected in 90% of the samples studied, with participants classified as having both FTD and motor neuron disease (MND) showing greater concentrations. While co-pathology and clinical symptom overlap of these disorders is being increasingly recognized, more studies are needed to quantify the overlap.

Study Highlights Complexities of ALS-FTD  Spectrum Disorders

ALS and FTD were previously considered separate disorders. But the 2011 discovery that the two disorders share mutations of the gene C9orf72 as the most common genetic cause established that they share some risk genes and a pathology often related to dysfunction of the protein TDP-43, and can even occur in the same person. However, due to the lack of biomarkers and the general difficulty of diagnosing the mixed symptomology, the only way to definitively diagnose FTD is through a brain autopsy.

Although co-pathology and overlap of these disorders are recognized, the frequency of overlap, or the frequency of FTD among people with an ALS or MND diagnosis, is still not fully clear. The authors emphasize the necessity of characterizing the subgroups of FTD and ALS with shared pathological and genetic features, which can help identify biomarkers to make diagnosis during life easier.  The researchers conducted an observational study to analyze FTD’s and ALS’s clinical, pathological, and genetic features.

The authors turned to the Hospital Clínic de Barcelona in Spain to obtain donated brain samples from 124 people who met the neuropathological criteria for a MND diagnosis. In addition to the researchers’ own analysis, data were available from the routine examinations that had been performed on the donated brains. Data was also available from the neurologists who cared for brain donors before they died, providing researchers with their medical histories.

ALS and MND Diagnosed More Accurately During Life than FTD-ALS

Of the 124 donors, the underlying disorder was identified as ALS for 80 people (64%), with the remaining 44 (36%) having FTD-ALS. Abnormal TDP-43 accumulations were discovered in 116 donors (94%), 12 of whom (10%) also had a pathology related to C9orf72, while five people (4%) had accumulations of FET proteins. As the authors note, this implies that there are several potential pathologies at play on the molecular level.

The authors found that 10 people (9%) in the FTD-ALS group never reported motor symptoms despite having neurodegeneration patterns suggestive of them. Initial motor symptoms to develop were mostly those consistent with MND and ALS, occurring in 86 people (70%), with ten (8%) showing signs of other disorders, and data being unavailable for four (3%). Cognitive or behavioral symptoms were primarily found in the FTD-ALS group, though nine (13%) in the MND/ALS group showed symptoms during follow-up, with five (6%) meeting FTD-ALS diagnostic criteria.

Genetically, a mutation related to ALS or FTD was found in 18 donors (15%), 12 of whom (10%) had a C9orf72 mutation, with the remainder having less common risk genes such as TAF15. Genetic mutations were more commonly associated with FTD-ALS than with MND or ALS alone, with 14 carriers in the FTD-ALS group and four carriers in the ALS group. In comparing the neuropathological diagnoses against diagnoses made during life, people with ALS were more likely to be correctly diagnosed than those with FTD-ALS (94% vs 61%).

“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 [studies],” first author Álvaro Carbayo told ALS News Today.

The authors note that the variability in the pathology and symptoms of FTD-ALS creates significant difficulty for researchers and clinicians, which suggests that FTD-ALS is underdiagnosed. The authors state that the broad spectrum of FTD-ALS pathologies and symptoms should prompt a more intensive search for biomarkers and accurate diagnostic tools. Currently, this topic is a priority for many researchers in the FTD and ALS spaces (a sentence or two here to indicate that ALLFTD and other studies are focused on this too).

AFTD is working to bridge the gap between FTD and ALS research to work towards a future free from the FTD-ALS disorder spectrum. AFTD collaborates with stakeholders in the ALS space to drive research and regularly hosts ALS experts at events to discuss their work.

Are you or a loved one concerned about potential symptoms of FTD-ALS? AFTD’s FTD-ALS diagnostisk checklista is a specialized tool for families and physicians to determine next steps. If you have questions about FTD-ALS, AFTD:s hjälplinje has the answers you need; contact the HelpLine at 1-866-507-7222 eller info@theaftd.org.