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

This Article 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 Palmert, M. R. Articles by Younkin, S. G. Search for Related Content PubMed PubMed Citation Articles by Palmert, M. R. Articles by Younkin, S. G.

Soluble derivatives of the ß amyloid protein precursor in cerebrospinal fluid

Alterations in normal aging and in Alzheimer's disease

Division of Neuropathology, Institute of Pathology, and Department of Pharmacology (M.R. Palmert, M. Usiak, and Dr. Younkin), Case Western Reserve University School of Medicine, Cleveland, OH; the Department of Neurology (Dr. Mayeux), Columbia University, College of Physicians and Surgeons, New York, NY; the Department of Psychiatry and Behavioral Sciences (Dr. Raskind), University of Washington, Seattle, WA; and the Neurology and Research Services (Dr. Tourtellotte), VAMC Wadsworth, Los Angeles, CA.

We isolated and sequenced a soluble 25 kDa amino-terminal derivative of the ß amyloid protein precursor (ßAPP) that is readily detected in human cerebrospinal fluid (CSF). In CSF samples from 24 Alzheimer's disease (AD) patients and 12 controls, we then quantitated this 25 kDa form as well as the 125 and 105 kDa derivatives that we previously identified. Our analysis shows (1) that, in AD, there is a significant decrease in the relative amount of the 105 kDa form and a corresponding significant increase in the relative amount of the 25 kDa form; (2) that these changes correlate with the mental status of the AD patients; and (3) that the same changes occur to a lesser extent in elderly as compared with young control patients. These observations indicate that processing of the ßAPP changes in normal individuals as they age and to a greater extent in those who develop AD. The changes in ßAPP derivatives that we have observed in CSF could have major implicataions because they may reflect fundamental mechanisms responsible for amyloid deposition and can be measured in living patients.

Address correspondence and reprint requests to Dr. S.G. Younkin, Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106.

Supported by USPHS grants AG06656 (S.G.Y.), AG02802 (R.M.), MH43444 (S.G.Y.), and 5T32GM0250 (M.R.P.), and grants from the State of Ohio (S.G.Y.) and the Parkinson's Disease Foundation.

Presented in part at the annual meeting of the Society for Neuroscience, Phoenix, AZ, October 1989, and at the annual meeting of the American Association of Neuropathologists, Dallas, TX, June 1989.

Received March 9, 1990. Accepted for publication in final form March 21, 1990.

This article has been cited by other articles:

				P. Porayette, M. J. Gallego, M. M. Kaltcheva, R. L. Bowen, S. Vadakkadath Meethal, and C. S. Atwood Differential Processing of Amyloid-{beta} Precursor Protein Directs Human Embryonic Stem Cell Proliferation and Differentiation into Neuronal Precursor Cells J. Biol. Chem., August 28, 2009; 284(35): 23806 - 23817. [Abstract] [Full Text] [PDF]

				K. Nishiyama, B. D. Trapp, T. Ikezu, R. M. Ransohoff, T. Tomita, T. Iwatsubo, I. Kanazawa, K. K. Hsiao, M. P. Lisanti, and T. Okamoto Caveolin-3 Upregulation Activates beta -Secretase-Mediated Cleavage of the Amyloid Precursor Protein in Alzheimer's Disease J. Neurosci., August 1, 1999; 19(15): 6538 - 6548. [Abstract] [Full Text] [PDF]

				S. C. Samuels, J. M. Silverman, D. B. Marin, E. R. Peskind, S. G. Younki, D. A. Greenberg, E. Schnur, J. Santoro, and K. L. Davis CSF beta-amyloid, cognition, and APOE genotype in Alzheimer's disease Neurology, February 1, 1999; 52(3): 547 - 547. [Abstract] [Full Text] [PDF]

				V. Y. H. Hook, C. Sei, S. Yasothornsrikul, T. Toneff, Y.-H. Kang, S. Efthimiopoulos, N. K. Robakis, and W. Van Nostrand The Kunitz Protease Inhibitor Form of the Amyloid Precursor Protein (KPI/APP) Inhibits the Proneuropeptide Processing Enzyme Prohormone Thiol Protease (PTP). COLOCALIZATION OF KPI/APP AND PTP IN SECRETORY VESICLES J. Biol. Chem., January 29, 1999; 274(5): 3165 - 3172. [Abstract] [Full Text] [PDF]

				Q. Guo, N. Robinson, and M. P. Mattson Secreted beta -Amyloid Precursor Protein Counteracts the Proapoptotic Action of Mutant Presenilin-1 by Activation of NF-kappa B and Stabilization of Calcium Homeostasis J. Biol. Chem., May 15, 1998; 273(20): 12341 - 12351. [Abstract] [Full Text] [PDF]

				R. D. Moir, T. Lynch, A. I. Bush, S. Whyte, A. Henry, S. Portbury, G. Multhaup, D. H. Small, R. E. Tanzi, K. Beyreuther, et al. Relative Increase in Alzheimer's Disease of Soluble Forms of Cerebral Abeta Amyloid Protein Precursor Containing the Kunitz Protease Inhibitory Domain J. Biol. Chem., February 27, 1998; 273(9): 5013 - 5019. [Abstract] [Full Text] [PDF]

				L. Gasparini, M. Racchi, G. Binetti, M. Trabucchi, S. B. Solerte, D. Alkon, R. Etcheberrigaray, G. Gibson, J. Blass, R. Paoletti, et al. Peripheral markers in testing pathophysiological hypotheses and diagnosing Alzheimer's disease FASEB J, January 1, 1998; 12(1): 17 - 34. [Abstract] [Full Text]

				O. Heinonen, H. Soininen, S. Syrjanen, H. Neittaanmaki, L. Paljarvi, O. Kosunen, K. Syrjanen, and P. Riekkinen Sr {beta}-Amyloid Protein Immunoreactivity in Skin Is Not a Reliable Marker of Alzheimer's Disease: An Autopsy-Controlled Study Arch Neurol, August 1, 1994; 51(8): 799 - 804. [Abstract] [PDF]