• Qin Chen, Bradley F Boeve, Nirubol Tosakulwong, Timothy Lesnick, Danielle Brushaber, Christina Dheel, Julie Fields, Leah Forsberg, Ralitza Gavrilova, Debra Gearhart, Dana Haley, Jeffrey L Gunter, Jonathan Graff-Radford, David Jones, David Knopman, Neill Graff-Radford, Ruth Kraft, Maria Lapid, Rosa Rademakers, Jeremy Syrjanen, Zbigniew K Wszolek, Howie Rosen, Adam L Boxer, and Kejal Kantarci.
• From the Department of Radiology (Q.C., J.L.G., K.K.), Department of Neurology (B.F.B., C.D., L.F., D.G., J.G.-R., D.J., D.K., R.K.), Department of Health Sciences Research (N.T., T.L., D.B., J.S.), Department of Psychology and Psychiatry (J.F., M.L.), Department of Clinical Genomic and Neurology (R.G.), Alzheimer's Disease Research Center (B.F.B., D.B., C.D., L.F., D.G., J.G.-R., D.J., D.K., R.K., R.R., K.K.), and Research Services (D.H.), Mayo Clinic, Rochester, MN; Department of Neurology (Q.C.), West China Hospital of Sichuan University, Chengdu, Sichuan; Departments of Neurology (N.G.-R., Z.K.W.) and Neuroscience (R.R.), Mayo Clinic, Jacksonville, FL; and Memory and Aging Center (H.R., A.L.B.), University of California San Francisco.
• Neurology. 2019 Aug 20; 93 (8): e758-e765.

ObjectiveTo determine the frontal lobe proton magnetic resonance spectroscopy (1H MRS) abnormalities in asymptomatic and symptomatic carriers of microtubule-associated protein tau (MAPT) mutations.MethodsWe recruited patients with MAPT mutations from 5 individual families, who underwent single voxel 1H MRS from the medial frontal lobe at 3T (n = 19) from the Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS) Study at the Mayo Clinic site. Asymptomatic MAPT mutation carriers (n = 9) had Frontotemporal Lobar Degeneration Clinical Dementia Rating Sum of Boxes (FTLD-CDR SOB) score of zero, and symptomatic MAPT mutation carriers (n = 10) had a median FTLD-CDR SOB score of 5. Noncarriers from healthy first-degree relatives of the patients were recruited as controls (n = 25). The demographic aspects and 1H MRS metabolite ratios were compared by use of the Fisher exact test for sex and linear mixed models to account for within-family correlations. We used Tukey contrasts for pair-wise comparisons.ResultsAsymptomatic MAPT mutation carriers had lower neuronal marker N-acetylaspartate (NAA)/creatine (Cr) (p = 0.001) and lower NAA/myo-inositol (mI) (p = 0.026) than noncarriers after adjustment for age. Symptomatic MAPT mutation carriers had lower NAA/Cr (p = 0.01) and NAA/mI (p = 0.01) and higher mI/Cr (p = 0.02) compared to noncarriers after adjustment for age. Furthermore, NAA/Cr (p = 0.006) and NAA/mI (p < 0.001) ratios decreased, accompanied by an increase in mI/Cr ratio (p = 0.001), as the ages of carriers approached and passed the age at symptom onset.ConclusionFrontal lobe neurochemical alterations measured with 1H MRS precede the symptom onset in MAPT mutation carriers. Frontal lobe 1H MRS is a potential biomarker for early neurodegenerative processes in MAPT mutation carriers.© 2019 American Academy of Neurology.

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