CHOLINERGIC ACTIVITY IN ALZHEIMER'S DISEASE

Project: Research project

Description

This project is designed to study the cholinergic system in the blood of
patients with Alzheimer's Disease and in the brain of a rat model of the
disease, aluminum poisoning. There have been brief reports of changes in
the erythrocyte choline levels, erythrocyte choline transport, erythrocyte
acetylcholinesterase activity and plasma acetylcholinesterase
pseudocholinesterase activities in patients with Alzheimer's Disease. The
present study will be unique in that we will make all of these measurements
in each sample. Subjects will be well documented cases from University
Hospital and will consist of controls, aged non-demented, and demented with
and without the diagnosis of Alzheimer's Disease. These results should
indicate the specificity and degree of biochemical changes occurring in the
blood of patients with Alzheimer's Disease. We will examine the data for
relationship among the biochemical measures and between biochemical and
clinical data. Patients will be re-examined and blood samples obtained at
least yearly to investigate the effects of the progressive deterioration of
Alzheimer's Disease on these biochemical measures. Confirmation of
preliminary evidence of changes in these blood samples will be followed by
investigations of possible biochemical mechanisms causing the changes.
Among these studies will be measurements of the kinetics of cholinesterase,
ion requirements of choline transport, choline transport in erythrocyte
ghosts and in "young" and "old" fractions of erythrocytes. We will also examine the effects of aluminum on cholinergic activity rat
brain because aluminum has been implicated as a causative factor in
Alzheimer's Disease. We will test this proposal by treating rats acutely
and chronically with aluminum followed by measurements of 14C-glucose
conversion to 14C02, 14C-acetylcholine and 14C-lipids in brain slices, high
affinity choline transport in synaptosomes, choline acetyltransferase,
muscarinic receptors and phosphatidylinositol turnover. We will emphasize
measurements that indicate the dynamics of the cholinergic system, such as
phosphatidylinositol turnover, choline uptake and acetylcholine synthesis
and release. We will also test the effects of drugs that alter cholinergic
activity on aluminum toxicity. These experiments should clarify whether or
not aluminum causes deficits in the cholinergic system similar to those
reported in patients with Alzheimer's Disease.
StatusFinished
Effective start/end date1/1/8512/31/87

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

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Choline
Aluminum
Cholinergic Agents
Alzheimer Disease
Erythrocytes
Acetylcholine
Choline O-Acetyltransferase
Synaptosomes
Cholinesterases
Brain
Muscarinic Receptors
Phosphatidylinositols
Poisoning
Ions
Lipids
Pharmaceutical Preparations

ASJC

  • Medicine(all)