Depression, hallucinations, and delusions are frequent complications of Alzheimer's disease (AD); therefore, AD may provide a model for studying the pathophysiology of these symptoms. Two recent finding support the utility of this approach: depression in AD is genetically related to depression occurring in major affective illness; and, in our preliminary studies, cases of AD with depression have a greater loss of nonadrenergic neurons of the locus coeruleus than cases of AD without depression, In Project 5, we propose to investigate the relationships between psychiatric symptoms in AD and the pathology in brainstem monoaminergic circuits. Cases of AD with or without depression and cases with or without psychosis will be prospectively matched for age of onset, duration of illness, and the score of the last Mini-Mental Status Examination. First, in depressed vs. nondepressed cases of AD, we will count noradrenergic neurons of locus coeruleus and serotoninergic neurons of nucleus raphe dorsalis and nucleus centralis superior. We predict that cases of AD with depression will have greater loss of neurons in specific regions of these nuclei than cases of AD without depression. Second, we will count dopaminergic neurons in several defined subnuclei within the ventral tegmental area in cases of AD with or without psychosis. We hypothesize that individuals with psychosis will have greater losses of these dopaminergic neurons than individuals without psychosis. Third, using transmitter-marker autoradiography and neurochemical techniques, we will correlate abnormalities in these brainstem nuclei with decrements in monoaminergic markers in target fields within the forebrain. By clarifying the relationships between psychiatric symptoms in AD and abnormalities of defined monoaminergic neurons, these studies may provide new insights into the pathophysiology of psychiatric disorders in AD.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Specialized Center (P50)
Project #
5P50AG005146-09
Application #
3802571
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Type
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
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