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Early neurotransmitters changes in prodromal frontotemporal dementia: A GENFI study
Enrico Premi1, Marta Pengo2, Irene Mattioli3
1Neurology, Department of Neurological and Vision Sciences, ASST Spedali Civili, Brescia, Italy.
Neurobiology of Disease
|March 10, 2023
Summary
Neurotransmitter deficits in Frontotemporal Dementia (FTD) are linked to brain changes. Early FTD stages show specific neurotransmitter pathway alterations, guiding potential symptomatic treatments.
Area of Science:
- Neuroscience
- Neuroimaging
- Genetics
Background:
- Neurotransmitter deficits in Frontotemporal Dementia (FTD) are poorly understood.
- Identifying these deficits in early disease stages is crucial for developing targeted symptomatic treatments.
Purpose of the Study:
- To investigate the relationship between brain structure and neurotransmitter systems in monogenic FTD.
- To explore neurotransmitter pathway alterations in both prodromal and symptomatic FTD stages.
Main Methods:
- Utilized the JuSpace toolbox for cross-modal correlation analysis.
- Integrated Magnetic Resonance Imaging (MRI) with nuclear imaging data for neurotransmitter systems (dopaminergic, serotonergic, etc.).
- Analyzed 392 mutation carriers (GRN, C9orf72, MAPT) and 276 healthy controls (HC), comparing grey matter volume (GMV) alterations.
Main Results:
- Prodromal C9orf72 FTD showed associations with dopamine and acetylcholine pathways.
- Prodromal MAPT FTD linked to dopamine and serotonin pathways; no significant findings in prodromal GRN FTD.
- Symptomatic FTD exhibited widespread involvement of dopamine, serotonin, glutamate, and acetylcholine pathways across all genetic subtypes.
Conclusions:
- This study offers insights into FTD disease mechanisms by indirectly assessing neurotransmitter deficits.
- Findings suggest potential therapeutic targets for FTD symptoms, particularly those related to social cognition and empathy.
