THE AGING BRAIN: IMMUNOHISTOLOGY AND BIOCHEMISTRY

  • Yen, Shu-Hui C (PI)

Project: Research project

Project Details

Description

This project is aimed at understanding the biology and molecular
pathogenesis of aging in the nervous system. Alzehimer's disease is the
most common organic dementia seen in old age. In this disease an important
histopathological lesion is the presence of neurofibrillary tangles which
contain mostly paired helical filaments. Antibodies raised against several normal neurofibrous proteins have been
used to study the molecular nature of tangles. Information available
indicates that tangles share antigenic determinants with neurofilament
protein and vimentin. It is unknown if additional elements are involved in
making tangles. Recently by immunization of mice with a partially purified
tangle fraction and subsequent hybridization of an immunized mouse spleen
cells with myeloma cells, we produced a monoclonal anti-tangle antibody.
This antibody does not recognize neurofilament in axons or vimentin in HeLa
cells but bind to HeLa cell nuclei and mitotic spindle. The identity of
this tangle-related antigen and the function of the antigen in cell
division will be one of the subjects of our continuing studies. In
addition, we proposed to immunize more mice with partially purified
neurofibrillary tangles and raise a panel of monoclonal antibodies against
different determinants of the tangles. These antibodies will be used to
determine if tangles contain pathologic specific components or additional
normal brain components, to provide further evidence that tangles and
neurofilament proteins and vimentin have common immunological properties
and to further purify tangles. A separate project funded previously concerns the distribution of brain
glial filament protein (GFP) in the peripheral nervous system (PNS). We
have demonstrated that in PNS the GFP is distributed primarily in Schwann
cells associated with unmyelinated axons and that the GFP of CNS and PNS
have common biochemical properties. In continuing studies, we propose to
determine if axons dictate the expression of GFP in Schwann cells. We will
use ultrastructural, immunohistochemical and biochemical techniques to
examine isolated nerve stumps, cross-anastomosed myelinated and
unmyelinated nerves of adult rats.
StatusFinished
Effective start/end date7/1/786/30/99

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $316,350.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)

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