Moncaster JA, Pineda R, Moir RD, Lu S, Burton MA, Ghosh JG, Ericsson M, Soscia SJ, Mocofanescu A, Folkerth RD, Robb RM, Kuszak JR, Clark JI, Tanzi RE, Hunter DG, Goldstein LE. Alzheimer's disease amyloid-beta links lens and brain pathology in Down syndrome. PLoS One. 2010;5(5):e10659. PubMed.
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University of Colorado Alzheimer’s and Cognition Center
There is a great need to develop a simple, non-invasive diagnostic test for Alzheimer disease. Many people, ourselves included, have tried to apply the old adage "The eyes…are the wyndowes of the mynde..." (T.Phaer; 1545 paraphrasing of Cicero) to the study of neurodegenerative disease. The paper by Moncaster and colleagues continues in this vein by assessing Alzheimer disease-linked pathology in the lenses of Down syndrome subjects’ eyes. Previous work by the same group (Goldstein et al., 2003) had shown amyloid deposits in lenses of AD subjects just as earlier studies had shown similar pathology in the retinas of AD subjects and mouse models of AD (e.g., Loffler et al, 1995; Frederise and Ren, 2002). Because trisomy 21/Down syndrome is easily identified, relatively common (~one in 750 live births), and inevitably leads to AD brain pathology by age 30-40, DS patients provide a special human population in which to study the earliest features of AD with the hope of gaining insight into the pathogenic pathway to the disease and of developing early diagnostics. In the current paper, Moncaster and his associate used Congo red birefringence, immunocytochemistry, and mass spectrometry peptide sequencing to demonstrate unequivocally that the Alzheimer Aβ peptide deposits early on (by age 22, and, at least by Western, by age two) in the lenses of DS patients in a manner essentially identical to the pathology observed in aged AD patients. Furthermore, in vitro experiments indicated that addition of Aβ to solubilized lens extracts increased protein aggregation as assayed by quasi-elastic light scattering. This result is interesting in light of previous work showing a direct interaction between αB-crystalin and Aβ that promotes Aβ neurotoxicity (Stege et al., 1999). Although the level of Aβ peptide in the lens is some fivefold less than in the DS or AD brain, the fact that an easily administered eye test for Alzheimer disease may come out of this work makes this paper particularly significant.
References:
Frederikse PH, Ren XO. Lens defects and age-related fiber cell degeneration in a mouse model of increased AbetaPP gene dosage in Down syndrome. Am J Pathol. 2002 Dec;161(6):1985-90. PubMed.
Goldstein LE, Muffat JA, Cherny RA, Moir RD, Ericsson MH, Huang X, Mavros C, Coccia JA, Faget KY, Fitch KA, Masters CL, Tanzi RE, Chylack LT, Bush AI. Cytosolic beta-amyloid deposition and supranuclear cataracts in lenses from people with Alzheimer's disease. Lancet. 2003 Apr 12;361(9365):1258-65. PubMed.
Löffler KU, Edward DP, Tso MO. Immunoreactivity against tau, amyloid precursor protein, and beta-amyloid in the human retina. Invest Ophthalmol Vis Sci. 1995 Jan;36(1):24-31. PubMed.
Stege GJ, Renkawek K, Overkamp PS, Verschuure P, van Rijk AF, Reijnen-Aalbers A, Boelens WC, Bosman GJ, de Jong WW. The molecular chaperone alphaB-crystallin enhances amyloid beta neurotoxicity. Biochem Biophys Res Commun. 1999 Aug 19;262(1):152-6. PubMed.
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