HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Correspondence: Submit a response Alert me when this article is cited Alert me when Correspondence are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Samuels, S. C. Articles by Davis, K. L. Search for Related Content PubMed PubMed Citation Articles by Samuels, S. C. Articles by Davis, K. L.

CSF beta-amyloid, cognition, and APOE genotype in Alzheimer’s disease

From the Department of Psychiatry (Drs. Samuels, Silverman, Marin, Greenberg, and Davis, and E. Schnur and J. Santoro), Mount Sinai School of Medicine, New York, NY; Department of Psychiatry and Behavioral Sciences (Dr. Peskind), University of Washington School of Medicine, and Geriatric Research, Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA; and Mayo Clinic (Dr. Younkin), Jacksonville, FL.

Address correspondence and reprint requests to Dr. Steven C. Samuels, Department of Psychiatry, Mount Sinai Medical Center, One Gustave L. Levy Place, Box 1230, New York, NY 10029.

OBJECTIVES: We examined the relationship between CSF amyloid beta peptide (Aß) concentration and AD severity in 31 probable AD patients and explored whether APOE genotype modifies this relationship.

BACKGROUND: Aß deposition in AD brains has been correlated with disease severity and with APOE-4 allele frequency. Few studies have examined the effects of APOE genotype on the relationship between CSF Aß and disease severity in an antemortem sample.

METHODS: Patients carried the clinical diagnosis of probable AD and did not have serious medical illness, current or past diagnosis of mood disorder, schizophrenia or alcoholism, or current psychotic features. The Mini-Mental State Examination (MMSE) was administered to the patient within 3 months of CSF collection. CSF was analyzed for Aß1-40 and Aß1-42 by sandwich ELISAs, and APOE genotype was determined by PCR run from blood. Correlations were performed between MMSE score and Aß1-40 and Aß1-42 concentrations while controlling for potential confounding variables.

RESULTS: CSF measures of Aß1-40 and Aß1-42 concentrations were correlated with each other (r = 0.56, df = 28, p < 0.01). CSF Aß1-40 and Aß1-42 concentrations were positively correlated with MMSE score. The negative association between CSF Aß measures and disease severity remained significant after controlling for age (Aß1-40 and MMSE score: r = 0.46, df = 28, p = 0.01; Aß1-42 and MMSE score: r = 0.35, df = 28, p = 0.05). Among the APOE-3/3 homozygotes there was a significant positive correlation only between Aß1-42 and MMSE score (Aß1-42, r = 0.94, p = 0.02; Aß1-40, r = 0.79, p = 0.11).

CONCLUSIONS: We hypothesize that an increased deposition of Aß in plaques results in decreased CSF Aß concentration. The stronger relationship between MMSE score and CSF Aß, specifically in APOE-3/3 homozygotes, suggests that patients with APOE-3/3 genotype may have different pathogenic mechanisms than the other genotypes for Aß deposition or clearance.

This article has been cited by other articles:

				M. I. Kester, A. E. van der Vlies, M. A. Blankenstein, Y.A.L. Pijnenburg, E. J. van Elk, P. Scheltens, and W. M. van der Flier CSF biomarkers predict rate of cognitive decline in Alzheimer disease Neurology, October 27, 2009; 73(17): 1353 - 1358. [Abstract] [Full Text] [PDF]

				A. E. van der Vlies, N. A. Verwey, F. H. Bouwman, M. A. Blankenstein, M. Klein, P. Scheltens, and W. M. van der Flier CSF biomarkers in relationship to cognitive profiles in Alzheimer disease Neurology, March 24, 2009; 72(12): 1056 - 1061. [Abstract] [Full Text] [PDF]

				D. M. Hartley, C. Zhao, A. C. Speier, G. A. Woodard, S. Li, Z. Li, and T. Walz Transglutaminase Induces Protofibril-like Amyloid {beta}-Protein Assemblies That Are Protease-resistant and Inhibit Long-term Potentiation J. Biol. Chem., June 13, 2008; 283(24): 16790 - 16800. [Abstract] [Full Text] [PDF]

				N. Ertekin-Taner, L. H. Younkin, D. M. Yager, F. Parfitt, M. C. Baker, S. Asthana, M. L. Hutton, S. G. Younkin, and N. R. Graff-Radford Plasma amyloid {beta} protein is elevated in late-onset Alzheimer disease families Neurology, February 19, 2008; 70(8): 596 - 606. [Abstract] [Full Text] [PDF]

				R. Squitti, G. Barbati, L. Rossi, M. Ventriglia, G. Dal Forno, S. Cesaretti, F. Moffa, I. Caridi, E. Cassetta, P. Pasqualetti, et al. Excess of nonceruloplasmin serum copper in AD correlates with MMSE, CSF {beta}-amyloid, and h-tau. Neurology, July 11, 2006; 67(1): 76 - 82. [Abstract] [Full Text] [PDF]

				E. Gomez-Tortosa, I. Gonzalo, S. Fanjul, M. J. Sainz, S. Cantarero, C. Cemillan, J. G. Yebenes, and T. del Ser Cerebrospinal Fluid Markers in Dementia With Lewy Bodies Compared With Alzheimer Disease Arch Neurol, September 1, 2003; 60(9): 1218 - 1222. [Abstract] [Full Text] [PDF]

				M. Riemenschneider, S. Wagenpfeil, J. Diehl, N. Lautenschlager, T. Theml, B. Heldmann, A. Drzezga, T. Jahn, H. Forstl, and A. Kurz Tau and A{beta}42 protein in CSF of patients with frontotemporal degeneration Neurology, June 11, 2002; 58(11): 1622 - 1628. [Abstract] [Full Text] [PDF]

				P. D. Mehta, T. Pirttila, S. P. Mehta, E. A. Sersen, P. S. Aisen, and H. M. Wisniewski Plasma and Cerebrospinal Fluid Levels of Amyloid {beta} Proteins 1-40 and 1-42 in Alzheimer Disease Arch Neurol, January 1, 2000; 57(1): 100 - 105. [Abstract] [Full Text] [PDF]