TG-1: a marker for neuronal nuclei in Alzheimer's disease

Abstract

TG-1 is a monoclonal antibody (mAb) raised against paired helical filaments purified from Alzheimer's Disease (AD) brain by immunoaffinity chromatography. By immunocytochemistry, TG-1 reveals abundant staining of neuronal nuclei in AD brain, but little or no staining in normal brain. TG-1 stained nuclei are observed in areas of AD brain with neurofibrillary pathology and in certain neurones that are not normally affected. Biochemical studies with TG-1 show antigens of 32–38 kDa in pellets and 50 kDa in supernatants from brain, with no obvious differences between normal and AD. TG-1 also recognizes an unusual structure, i.e., a ‘starburst’ in brain tissue from AD and elderly normals. Starbursts are not immunoreactive for the astrocytic marker, glial fibrillary acidic protein, and are not associated with amyloid. Widespread nuclear staining is observed with TG-1 in rat brain, and the immunoreactive antigens in purified nuclei are similar to those in human brain. Thus, TG-1 identifies neuronal nuclear antigens that are altered in AD, and provides a new avenue for studying pathogenic mechanisms in the disease.

Keywords

• dentate gyrus granule cells
• microtubule-associated tau protein
• neurofibrillary pathology
• nuclear protein kinases
• paired helical filaments