Total brain N-acetylaspartate: a new measure of disease load in MS.
OBJECTIVE
To quantitate the extent of neuronal cell loss in MS via the whole brain's N-acetylaspartate (NAA) concentration (WBNAA).


METHODS
Because NAA is assumed to be present only in neuronal cell bodies and their axons, we measured WBNAA as a marker for viable neurons in 12 patients (9 women and 3 men, 26 to 53 years of age) suffering from relapsing-remitting (RR) MS for at least 5 years and compared them with 13 age- and sex-matched normal controls. Total brain NAA was determined with proton MR spectroscopy, and WBNAA was obtained by dividing it by the total brain volume, calculated from high resolution MRI.


RESULTS
The WBNAA of the RR MS patients was lower than their matched controls (p<0.005). This difference was greater among older than younger subjects. The linear prediction equations of WBNAA with age indicate a faster, x10, decline in the patients, approximately 0.8% per year of age (p = 0.022).


CONCLUSIONS
The age-dependent decrease of whole brain N-acetylaspartate (WBNAA) in the patients suggests that progressive neuronal cell loss is a cardinal feature of this disease. WBNAA offers a quick, highly reproducible measure of disease progression and may be an important marker of treatment efficacy in MS as well as other neurodegenerative diseases.
Gonen
O
O
Division of Medical Science, Fox Chase Cancer Center, Philadelphia, PA, USA.
Catalaa
I
I
Babb
J S
JS
Ge
Y
Y
Mannon
L J
LJ
Kolson
D L
DL
Grossman
R I
RI
D000293:Adolescent; D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D015415:Biomarkers; D001921:Brain / Q000378:metabolism*; D002470:Cell Survival; D018450:Disease Progression; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D012016:Reference Values; D015203:Reproducibility of Results; D012720:Severity of Illness Index
D015415:Biomarkers; D001224:Aspartic Acid; C000179:N-acetylaspartate