P1–128: Non–invasive early detection of beta–amyloid molecular pathology by quasi–elastic light scattering in vivo
Year: 2006
Type: article
Study design: Case Report
Abstract: Sensitive, specific, objective diagnostic tests for Alzheimer's disease (AD) are urgently needed for efficient drug development and effective clinical use of emerging therapies. Enabling AD diagnostic technology will accelerate preclinical drug discovery, streamline clinical testing, and facilitate therapeutic intervention. Patient care will be enhanced by an objective means to assess AD risk, establish early diagnosis/prognosis, initiate therapeutic intervention, track disease progression, and monitor treatment response. We previously reported discovery of beta–amyloid peptides, AD–associated amyloid pathology, and unusual co–localizing equatorial supranuclear cataracts in the ocular lenses of patients with AD but not in those without the disorder [Lancet, 2003]. We recently discovered and characterized similar beta–amyloid lens pathology in patients with Down syndrome and in Tg2576 transgenic mice. These findings provide the first evidence of AD–associated beta–amyloid pathology outside the brain and support a direct molecular link between AD–associated pathology in brain and lens. To develop and test novel laser technology for early quantitative detection/monitoring of AD–associated amyloid lens pathology in vivo. Non–invasive infrared quasi–elastic light scattering (QLS), stereophotomicroscopy, quantitative western blot, ELISA. We developed in vivo QLS technology to quantitatively assess amyloid–mediated lens protein aggregation within discrete lens subregions. The instrument is easy to use, reliable, and extremely sensitive. We tested this non–invasive technology in non–anesthetized Tg2576 and age–matched WT control mice. Non–invasive lens QLS measurements (right–angle scattering intensity, It90) completely differentiated Tg2576 vs age–matched WT controls at 10 months of age, when cerebral and lenticular amyloid pathology are minimal. Preclinical testing using systemic or topical administration of a lipophilic amyloid–binding fluorescent ligand demonstrates anatomically localized amyloid–associated lenticular fluorescence in vivo. Non–invasive quantitative laser technologies hold promise for early diagnostic assessment of AD–associated pathology in vivo. NIA (AG024792, LG), NIGMS (GM075986); Alzheimer's Association, Massachusetts Lion's Eye Research Fund, MA Alzheimer's Disease Research Center, Brigham & Women's Hosp, anonymous foundations.
Source: Alzheimer s & Dementia
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4214805502