Diagnosing Alzheimer's Disease

About

Alzheimer's disease is awidespread progressive dementia affecting a significant fraction of the elderlypopulation. Current estimates indicate that three million Americans and 15million people worldwide suffer from this brain-destroying condition. Whilethere have been significant advances in research over the last five years, theprimary pathology of the disorder remains unknown. The behavioral symptoms ofAlzheimer's disease are well known, and include loss of memory and cognitivefunction. At the present time,there is no established test for diagnosing Alzheimer's disease typically, adiagnosis of Alzheimer's disease is made after autopsy. Neither is there asystem to quantify the neuropathological changes associated with Alzheimer'sdisease nor a method to screen and evaluate potential therapies that mayinhibit the development of amyloid plaques. In view of the present lack of knowledgeabout the development and progression of Alzheimer's disease, there is clearlya pressing need for reliable in-vivo non-invasive diagnostic markers of diseaseand disease progression. Description of the Project: Researchers at NYU have developed a method fordiagnosing Alzheimer's disease by early detection of amyloid plaques in-vivousing magnetic resonance imaging. This method relies on using an Aß-1-40peptide bound to a contrast agent which, upon injection, binds selectively toAß. This material is injected systemically with mannitol which acts totransiently open the blood-brain barrier such that pre-Aß deposits and amyloidplaques can be visualized under MRI conditions routinely used clinically. This technology has beendemonstrated in a transgenic mouse model for Alzheimer's disease. Followinginjection of mice with the contrast agent bound to Aß1-40 and mannitol, MRIdetected the presence of both amyloid and pre-amyloid plaques. The injectedmice showed good correlation with the corresponding immunohistochemicallystained brain sections for amyloid. Applications: This technology is useful for diagnosingAlzheimer's disease in-vivo at the earliest stage. Once there is an effectivetherapy for Alzheimer's disease, this technology could be used in combinationto monitor the effectiveness of a particular therapy. Thus, this technologypermits early detection of amyloid lesions, when they may be most amenable totherapeutic intervention.