bf-227 and 2-(4--(methylamino)phenyl)-6-hydroxybenzothiazole

Although a battery of neuropsychological tests is often used in making a clinical diagnosis of Alzheimer's disease (AD), definitive diagnosis still relies on pathological evaluation at autopsy. The identification of AD biomarkers may allow for a less invasive and more accurate diagnosis as well as serve as a predictor of future disease progression and treatment response. Importantly, biomarkers may also allow for the identification of individuals who are already developing the underlying pathology of AD such as plaques and tangles yet who are not yet demented, i.e. "preclinical" AD. Attempts to identify biomarkers have included fluid and imaging studies, with a number of candidate markers showing significant potential. More recently, better reagent availability and novel methods of assessment have further spurred the search for biomarkers of AD. This review will discuss promising fluid and imaging markers to date.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Aniline Compounds; Animals; Benzoxazoles; Biomarkers; Brain; Cerebrovascular Circulation; Humans; Isoprostanes; Microglia; Nitriles; Protease Nexins; Radiography; Receptors, Cell Surface; Regional Blood Flow; Stilbenes; tau Proteins; Thiazoles

This paper reviews the progress in developing amyloid imaging ligands to be used to measure amyloid in vivo in the brain of patients with Alzheimer's disease.. Four radioligands, [18F] 1,1-dicyano-2-[6-(dimethylamino)-2-naphtalenyl] propene or 18F-FDDNP, N-methyl [11C] 2-(4'-methylaminophenyl)-6-hydroxy-benzothiasole or 11C-PIB, 4-N-methylamino-4'-hydroxystilbene [11C] or SB13 and 2-(2-[2-dimethylaminothiazol-5-yl]ethenyl)-6-(2-[fluoro]ethoxy)benzoxazole or 11C-BF-227, have so far been studied in Alzheimer's disease patients and age-matched healthy controls by PET. A robust difference was observed between PIB retention in mild patients and controls. A 2-year follow-up study in mild patients showed a stable level of PIB retention and a decrease in cerebral glucose metabolism and cognition. 18F-FDDNP showed less difference between Alzheimer's disease patients and controls compared with PIB. Both ligands have detected increases in amyloid in the brain of patients with mild cognitive impairment.. The new PET amyloid imaging technique is a breakthrough in understanding the pathophysiological mechanisms and time course in amyloid deposits in the brain. The technique will enable early detection of Alzheimer's disease. PET amyloid imaging should be used in the evaluation of new antiamyloid therapies.

Topics: Alzheimer Disease; Amyloid; Aniline Compounds; Animals; Benzothiazoles; Benzoxazoles; Brain; Carbon Radioisotopes; Fluorine Radioisotopes; Humans; Longitudinal Studies; Mice; Mice, Transgenic; Molecular Structure; Positron-Emission Tomography; Radiopharmaceuticals; Thiazoles