Relationships among Cortical Glutathione Levels, Brain Amyloidosis, and Memory in Healthy Older Adults Investigated In Vivo with1H-MRS and Pittsburgh Compound-B PET.
OBJECTIVE
Oxidative stress has been implicated as an important pathologic mechanism in the development of Alzheimer disease. The purpose of this study was to assess whether glutathione levels, detected noninvasively with proton MR spectroscopy, are associated with brain amyloidosis and memory in a community-dwelling cohort of healthy older adults.


METHODS
Fifteen cognitively healthy subjects were prospectively enrolled in this study. All subjects underwent1H-MR spectroscopy of glutathione, a positron-emission tomography scan with an amyloid tracer, and neuropsychological testing by using the Repeatable Battery for the Assessment of Neuropsychological Status. Associations among glutathione levels, brain amyloidosis, and memory were assessed by using multivariate regression models.


RESULTS
Lower glutathione levels were associated with greater brain amyloidosis in the temporal (P= .03) and parietal (P= .05) regions, adjusted forapolipoprotein Eε4 carrier status. There were no significant associations between glutathione levels and cognitive scores.


CONCLUSIONS
This study found an association between cortical glutathione levels and brain amyloidosis in healthy older adults, suggesting a potential role for1H-MR spectroscopy measures of glutathione as a noninvasive biomarker of early Alzheimer disease pathogenesis.
From the Departments of Radiology (G.C.C., X.M., G.K., E.C., S.P., S.V., D.C.S.) gcc9004@med.cornell.edu.
G C
http://orcid.org/0000-0001-9925-0816
GC
Chiang
From the Departments of Radiology (G.C.C., X.M., G.K., E.C., S.P., S.V., D.C.S.).
X
http://orcid.org/0000-0003-2274-8282
X
Mao
From the Departments of Radiology (G.C.C., X.M., G.K., E.C., S.P., S.V., D.C.S.).
G
http://orcid.org/0000-0002-8455-4822
G
Kang
From the Departments of Radiology (G.C.C., X.M., G.K., E.C., S.P., S.V., D.C.S.).
E
http://orcid.org/0000-0003-3269-3457
E
Chang
From the Departments of Radiology (G.C.C., X.M., G.K., E.C., S.P., S.V., D.C.S.).
S
http://orcid.org/0000-0002-3284-2603
S
Pandya
From the Departments of Radiology (G.C.C., X.M., G.K., E.C., S.P., S.V., D.C.S.).
S
http://orcid.org/0000-0002-6638-3695
S
Vallabhajosula
Neurology (R.I., L.D.R.), Weill Cornell Medical College, NewYork-Presbyterian Hospital, New York, New York.
R
http://orcid.org/0000-0002-0949-6204
R
Isaacson
Neurology (R.I., L.D.R.), Weill Cornell Medical College, NewYork-Presbyterian Hospital, New York, New York.
L D
http://orcid.org/0000-0003-3959-9682
LD
Ravdin
From the Departments of Radiology (G.C.C., X.M., G.K., E.C., S.P., S.V., D.C.S.).
D C
http://orcid.org/0000-0001-9452-2245
DC
Shungu
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis; D000686:Amyloidosis / Q000453:epidemiology / Q000378:metabolism*; D000814:Aniline Compounds; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D005978:Glutathione / Q000032:analysis*; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods; D066244:Proton Magnetic Resonance Spectroscopy / Q000379:methods; D013844:Thiazoles
C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D000814:Aniline Compounds; D013844:Thiazoles; D005978:Glutathione