P1‐379: In vivo detection of Alzheimer's disease‐linked Aβ peptide accumulation in the lens
Year: 2008
Type: article
Abstract: Sensitive, specific, objective diagnostic tests for Alzheimer disease (AD) are urgently needed for efficient drug development and effective clinical use of emerging therapies. Enabling AD diagnostic technology will enhance patient care 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 (Aβ) peptides, AD-associated amyloid pathology, and unusual co-localizing supranuclear cataracts in the lenses of patients with AD but not in those without the disorder [Lancet, 2003]. We then discovered similar Aβ pathology in Tg2576 transgenic mice. These findings provide the first evidence of AD-associated Aβ pathology outside the brain and support a direct molecular link between AD-associated pathology in brain and lens. Non-invasive infrared quasi-elastic light scattering (QLS), stereophotomicroscopy, trypic digest sequencing, immunohistochemistry, immunogold electron microscopy, quantitative western blot, ELISA. We developed in vivo QLS technology to quantitatively assess Aβ-mediated lens protein aggregation within discrete lens subregions. The instrument is easy to use, reliable, and extremely sensitive. We tested this noninvasive technology in non-anesthetized Tg2576 and age-matched Wt control mice. Non-invasive lens QLS measurements completely differentiated Tg2576 vs age-matched Wt controls at 10 months of age, when brain and lens amyloid pathology was minimal. We are now generating second-generation instruments that use fluorescent agents in vivo. Non-invasive quantitative laser technologies hold promise for early diagnostic assessment of AD-associated pathology in vivo.
Source: Alzheimer s & Dementia
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2033788720