Project Details


Background Many people with Alzheimer's often experience depression, especially during the early and middle stages. Another behavioral symptom, apathy (the loss of motivation) may be commonly experienced in mild to moderate stages of Alzheimer's, and this symptom increases severity as the dementia progresses. These neuropsychiatric symptoms may impact quality of life for individuals with Alzheimer's, yet not much is understood about them. Researchers are trying to understand the biological underpinnings by which these behavioral symptoms may be associated with individuals in Alzheimer's. One of the approaches to understand the biological mechanisms may be to look for genes throughout the entire genome (a person's complete set of genes) that may be associated with these behavioral symptoms observed in Alzheimer's. Research Plan Dr. Kiran Girdhar and colleagues will study brain tissue samples from 1264 individuals with Alzheimer's and psychiatric illnesses, from the Mount Sinai Brain Bank. As a first step, the researchers will study the tissue samples to identify major brain cells including nerve cells, microglia, the primary immune cells of the brain (microglia serve as one of the brain's first defenses against nerve cell damage), oligodendrocytes (type of brain cells which help nerve cells communicate with one another) and other major brain cell types. Subsequently, the researchers will study the transcriptome of these different brain cell types. The transcriptome is a collection of all gene readouts within the cell. The study of transcriptome reveals which genes are turned 'on' and 'off' in a given cell in response to their environment or disease state. In particular, the researchers will perform a sex-specific study of the gene readouts of cells taken from these brain tissues. Dr. Girdhar believes that these readouts may help identify changes in certain genes that may be associated with psychiatric symptoms. Impact The study results may help understand the biology of the psychiatric symptoms observed in Alzheimer's. In the long term, this study may help clarify whether these behavioral symptoms observed in Alzheimer's may be the same or different from people with severe mental illnesses and may give rise to new therapeutic approaches.
Effective start/end date1/01/21 → …


  • Alzheimer's Association


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