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Relations between brain tissue loss, CSF biomarkers, and the ApoE genetic profile: a longitudinal MRI study.
Neurobiol Aging 2010; 31(8):1340-54NA

Abstract

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.

Authors+Show Affiliations

Center for Imaging of Neurodegenerative Diseases, Department of Veterans Affairs Medical Center, San Francisco, CA 94121, United States. duygu.tosun@ucsf.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

20570401

Citation

Tosun, Duygu, et al. "Relations Between Brain Tissue Loss, CSF Biomarkers, and the ApoE Genetic Profile: a Longitudinal MRI Study." Neurobiology of Aging, vol. 31, no. 8, 2010, pp. 1340-54.
Tosun D, Schuff N, Truran-Sacrey D, et al. Relations between brain tissue loss, CSF biomarkers, and the ApoE genetic profile: a longitudinal MRI study. Neurobiol Aging. 2010;31(8):1340-54.
Tosun, D., Schuff, N., Truran-Sacrey, D., Shaw, L. M., Trojanowski, J. Q., Aisen, P., ... Weiner, M. W. (2010). Relations between brain tissue loss, CSF biomarkers, and the ApoE genetic profile: a longitudinal MRI study. Neurobiology of Aging, 31(8), pp. 1340-54. doi:10.1016/j.neurobiolaging.2010.04.030.
Tosun D, et al. Relations Between Brain Tissue Loss, CSF Biomarkers, and the ApoE Genetic Profile: a Longitudinal MRI Study. Neurobiol Aging. 2010;31(8):1340-54. PubMed PMID: 20570401.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Relations between brain tissue loss, CSF biomarkers, and the ApoE genetic profile: a longitudinal MRI study. AU - Tosun,Duygu, AU - Schuff,Norbert, AU - Truran-Sacrey,Diana, AU - Shaw,Leslie M, AU - Trojanowski,John Q, AU - Aisen,Paul, AU - Peterson,Ronald, AU - Weiner,Michael W, AU - ,, Y1 - 2010/06/08/ PY - 2010/02/16/received PY - 2010/04/26/revised PY - 2010/04/27/accepted PY - 2010/6/24/entrez PY - 2010/6/24/pubmed PY - 2011/3/30/medline SP - 1340 EP - 54 JF - Neurobiology of aging JO - Neurobiol. Aging VL - 31 IS - 8 N2 - 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. SN - 1558-1497 UR - https://www.unboundmedicine.com/medline/citation/20570401/Relations_between_brain_tissue_loss_CSF_biomarkers_and_the_ApoE_genetic_profile:_a_longitudinal_MRI_study_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0197-4580(10)00205-8 DB - PRIME DP - Unbound Medicine ER -