Cerebral changes and cerebrospinal fluid beta-amyloid in Alzheimer's disease: a study with quantitative magnetic resonance imaging.
Pathological and biochemical studies indicate that beta-amyloid (betaA4) deposition is a hallmark in the pathogenesis of Alzheimer's disease (AD). Neuroimaging studies demonstrate that the respective cerebral changes primarily strike the temporal lobe and the amygdala-hippocampus complex and may be reliably assessed using quantitative magnetic resonance imaging (MRI). Therefore one may expect that reduced betaA4-levels are significantly correlated with measures of the temporal lobe rather than global cerebral atrophy in AD patients. To test this hypothesis in a clinical study, cerebrospinal fluid concentrations of total betaA4 and its major C-terminal variations betaA4 1-40 and betaA4 1-42 were compared with cerebral changes as assessed by quantitative magnetic resonance imaging (MRI). Significantly (P< 0.05) reduced betaA4 1-40 and betaA4 1-42 levels were found in the AD patients (17 female; six male; AD/NINCDS-ADRDA-criteria) in comparison to the patients with major depression (seven female; two male; DSM-III-R). Within the AD group, betaA4 and betaA4 1-42 levels were significantly correlated with the volume of the temporal lobes (r= 0.46 and r= 0.48, respectively) but none of the other volumetric measures. These findings indicate that changes in cerebral betaA4 levels contribute to temporal lobe atrophy in AD and support the possibility that betaA4 is central to the etiology of AD.
Schröder
J
J
Section of Geriatric Psychiatry, University of Heidelberg, Germany. Johannes_schroeder@krzmail.krz.uni-heidelberg.de
Pantel
J
J
Ida
N
N
Essig
M
M
Hartmann
T
T
Knopp
M V
MV
Schad
L R
LR
Sandbrink
R
R
Sauer
H
H
Masters
C L
CL
Beyreuther
K
K
D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid / Q000378:metabolism*; D000704:Analysis of Variance; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D003866:Depressive Disorder / Q000134:cerebrospinal fluid / Q000378:metabolism*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D010446:Peptide Fragments / Q000134:cerebrospinal fluid / Q000378:metabolism; D012044:Regression Analysis; D013702:Temporal Lobe / Q000378:metabolism / Q000473:pathology
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)