NEUROPEPTIDE/CHOLINERGIC FUNCTION/ALZHEIMERS DISEASE

Project: Research project

Project Details

Description

Alzheimer's Disease (AD), a neuropsychiatric disorder, is characterized by
severe morbidity and is one of the leading causes of death in the elderly
in the United States. It comprises more than 50% of the cases of
dementia. Although considerable progress has been made in the genetics,
neurochemical pathology, neuropsychology, and neuroanatomy of AD, little
is available in the way of treatment, with the exception of the recent FDA
approval of an acetylcholinesterase inhibitor, which is helpful only in a
minority of patients. This revised competitive renewal application seeks
to build upon our progress in characterizing the neurochemical pathology
of neurons containing neuropeptides and other neurotransmitters in AD.
The major focus of this application is intensive scrutiny of the nature of
the pathological involvement of neurons containing corticotropin-releasing
factor (CRF) in AD. Our group was the first to describe the marked
reduction in CRF immunoreactivity in post-mortem brain tissue in patients
with AD, and this finding has been widely confirmed. In the present
application, we seek to scrutinize this finding more closely by
measurement of several indices of CRF neuronal function in post-mortem
brain tissue in AD and in controls. These measures include: CRF
immunoreactivity, CRF receptor density and affinity, mRNA expression for
both CRF and the CRF receptor, measurement of the concentration and
expression of the newly discovered CRF binding protein, as well as
measures of intracellular signal transduction in response to CRF. In
addition, in view of the many reports of widespread serotonergic and
noradrenergic neuronal dysfunction in AD, we shall utilize newly available
antibodies to the 5-HT and NE transporters to determine the cellular
localization and quantify the presynaptic 5-HT and NE transporter proteins
in post-mortem brain samples. The resultant data will also provide novel
information on the relationship between the pathological involvement of
these three neurotransmitter systems in AD. Taken together, these
experiments will further our understanding of the neurochemical pathology
of AD and provide the basis for the development of novel therapies for
this disorder.
StatusFinished
Effective start/end date1/1/9011/30/99

Funding

  • National Institute of Mental Health
  • National Institute of Mental Health
  • National Institute of Mental Health
  • National Institute of Mental Health
  • National Institute of Mental Health
  • National Institute of Mental Health
  • National Institute of Mental Health
  • National Institute of Mental Health
  • National Institute of Mental Health

Fingerprint

Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.