Regional brain metabolite abnormalities in inherited prion disease and asymptomatic gene carriers demonstrated in vivo by quantitative proton magnetic resonance spectroscopy.
BACKGROUND
Inherited prion diseases are caused by mutations in the gene which codes for prion protein (PrP), leading to proliferation of abnormal PrP isomers in the brain and neurodegeneration; they include Gerstmann-Sträussler-Scheinker disease (GSS), fatal familial insomnia (FFI) and familial Creutzfeldt-Jakob disease (fCJD).


METHODS
We studied two patients with symptomatic inherited prion disease (P102L) and two pre-symptomatic P102L gene carriers using quantitative magnetic resonance spectroscopy (MRS). Short echo time spectra were acquired from the thalamus, caudate region and frontal white matter, metabolite levels and ratios were measured and z-scores calculated for individual patients relative to age-matched normal controls. MRS data were compared with structural magnetic resonance imaging.


RESULTS
One fCJD case had generalised atrophy and showed increased levels of myo-inositol (MI) in the thalamus (z=3.7). The other had decreased levels of N-acetylaspartate (z=4) and diffuse signal abnormality in the frontal white matter. Both asymptomatic gene carriers had normal imaging, but increased frontal white matter MI (z=4.3, 4.1), and one also had increased MI in the caudate (z=5.3).


CONCLUSIONS
Isolated MI abnormalities in asymptomatic gene carriers are a novel finding and may reflect early glial proliferation, prior to significant neuronal damage. MRS provides potential non-invasive surrogate markers of early disease and progression in inherited prion disease.
Waldman
A D
AD
Dementia Research Group, Department of Neurodegenerative Disease, Institute of Neurology, University College London, Queen Square, London, WC1 3BG, UK. waldman@dementia.ion.ucl.ac.uk
Cordery
R J
RJ
MacManus
D G
DG
Godbolt
A
A
Collinge
J
J
Rossor
M N
MN
D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D016022:Case-Control Studies; D003401:Creatine / Q000378:metabolism; D005260:Female; D006579:Heterozygote; D006801:Humans; D007294:Inositol / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D017096:Prion Diseases / Q000235:genetics* / Q000378:metabolism*; D011328:Prions / Q000235:genetics*
D011328:Prions; D001224:Aspartic Acid; D007294:Inositol; C000179:N-acetylaspartate; D003401:Creatine