Identification of amyloid plaques in retinas from Alzheimer's patients and noninvasive in vivo optical imaging of retinal plaques in a mouse model

Noninvasive monitoring of beta-amyloid (A beta) plaques, the neuropathological hallmarks of Alzheimer's disease (AD), is critical for AD diagnosis and prognosis. Current visualization of A beta plaques in brains of live patients and animal models is limited in specificity and resolution. The retina as an extension of the brain presents an appealing target for a live, noninvasive optical imaging of AD if disease pathology is manifested there. We identified retinal A beta plaques in postmortem eyes from AD patients (n = 8) and in suspected early stage cases (n=5), consistent with brain pathology and clinical reports; plaques were undetectable in age-matched non-AD individuals (n = 5). In APP(SWE)/PS1(Delta E9) transgenic mice (AD-Tg; n = 18) but not in non-Tg wt mice (n = 10), retinal A beta plaques were detected following systemic administration of curcumin, a safe plaque-labeling fluorochrome. Moreover, retinal plaques were detectable earlier than in the brain and accumulated with disease progression. An immune-based therapy effective in reducing brain plaques, significantly reduced retinal A beta plaque burden in immunized versus non-immunized AD mice (n = 4 mice per group). In live AD-Tg mice (n = 24), systemic administration of curcumin allowed noninvasive optical imaging of retinal A beta plaques in vivo with high resolution and specificity; plaques were undetectable in non-Tg wt mice (n = 11). Our discovery of A beta specific plaques in retinas from AD patients, and the ability to noninvasively detect individual retinal plaques in live AD mice establish the basis for developing high-resolution optical imaging for early AD diagnosis, prognosis assessment and response to therapies. (C) 2010 Elsevier Inc. All rights reserved.