Relations between brain tissue loss, CSF biomarkers, and the ApoE genetic profile: a longitudinal MRI study.
Previously it was reported that Alzheimer's disease (AD) patients have reduced beta amyloid (Abeta(1-42)) and elevated total tau (t-tau) and phosphorylated tau (p-tau(181p)) in the cerebrospinal fluid (CSF), suggesting that these same measures could be used to detect early AD pathology in healthy elderly individuals and those with mild cognitive impairment (MCI). In this study, we tested the hypothesis that there would be an association among rates of regional brain atrophy, the CSF biomarkers Abeta(1-42), t-tau, and p-tau(181p) and apolipoprotein E (ApoE) epsilon4 status, and that the pattern of this association would be diagnosis-specific. Our findings primarily showed that lower CSF Abeta(1-42) and higher tau concentrations were associated with increased rates of regional brain tissue loss and the patterns varied across the clinical groups. Taken together, these findings demonstrate that CSF biomarker concentrations are associated with the characteristic patterns of structural brain changes in healthy elderly and mild cognitive impairment subjects that resemble to a large extent the pathology seen in AD. Therefore, the finding of faster progression of brain atrophy in the presence of lower Abeta(1-42) levels and higher tau levels supports the hypothesis that CSF Abeta(1-42) and tau are measures of early AD pathology. Moreover, the relationship among CSF biomarkers, ApoE epsilon4 status, and brain atrophy rates are regionally varying, supporting the view that the genetic predisposition of the brain to beta amyloid and tau mediated pathology is regional and disease stage specific.
Tosun
Duygu
D
Center for Imaging of Neurodegenerative Diseases, Department of Veterans Affairs Medical Center, San Francisco, CA 94121, United States. duygu.tosun@ucsf.edu
Schuff
Norbert
N
Truran-Sacrey
Diana
D
Shaw
Leslie M
LM
Trojanowski
John Q
JQ
Aisen
Paul
P
Peterson
Ronald
R
Weiner
Michael W
MW
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000235:genetics / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D053327:Apolipoprotein E4 / Q000096:biosynthesis / Q000235:genetics*; D001284:Atrophy; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000473:pathology*; D003072:Cognition Disorders / Q000134:cerebrospinal fluid / Q000235:genetics / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D011446:Prospective Studies; D016875:tau Proteins / Q000134:cerebrospinal fluid*
D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins