Brain MR Spectroscopy Changes Precede Frontotemporal Lobar Degeneration Phenoconversion in Mapt Mutation Carriers.

Area of Science:

• Neuroimaging
• Biomarkers
• Neurodegenerative Diseases

Background:

• MAPT mutations are associated with neurodegenerative conditions.
• Early detection of neurodegeneration in asymptomatic carriers is crucial.
• Understanding disease progression trajectories is key for therapeutic development.

Purpose of the Study:

• To longitudinally investigate changes in 1H MRS measurements in asymptomatic MAPT mutation carriers.
• To determine the timing of accelerated neurochemical alterations during disease progression.
• To assess the utility of 1H MRS in monitoring asymptomatic carriers.

Main Methods:

• Longitudinal follow-up of eight MAPT mutation carriers transitioning from asymptomatic to symptomatic disease.
• Average follow-up of 7.75 years with 60 1H MRS examinations.
• Linear mixed models and flex point analysis to estimate metabolite change rates and acceleration points.

Main Results:

• The NAA/mI ratio decrease accelerated 2.09 years before symptom onset.
• The mI/Cr ratio, a glial marker, accelerated 1.86 years before symptom onset.
• These neurochemical alterations continued to decline post-acceleration.

Conclusions:

• Longitudinal 1H MRS shows potential for monitoring neurodegenerative progression in MAPT carriers.
• Neurochemical alterations accelerate significantly prior to clinical symptom manifestation.
• 1H MRS can aid in early detection and tracking of disease in asymptomatic individuals.