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Abstract Details

Efficacy Difference of Antipsychotics in Alzheimer's Disease and Schizophrenia: Explained with Network Efficiency and Pathway Analysis Methods
Aging, Dementia, and Behavioral Neurology
Aging and Dementia Posters (7:00 AM-5:00 PM)
084

To explore the molecular mechanism of difference between Alzheimer’s disease (AD) with psychosis (AD+P) and schizophrenia in order and find reasons for the modest efficacy of antipsychotics in AD+P.
Psychotic symptoms, i.e., delusions and hallucinations, are frequent complications of AD. About 50% of AD patients will develop psychotic symptoms and these patients will experience more rapid cognitive decline than AD patients without psychosis (AD-P). However, no medication has been approved by FDA for AD+P specifically, and antipsychotics are widely used and recommended by geriatric experts. Unfortunately, antipsychotics have demonstrated modest efficacy in managing psychosis in dementia individuals, increasing their sensitivity to adverse events.
In this study, we compared the similarities and differences between the genetic variations/genes associated with AD+P and schizophrenia. We then constructed two protein-protein interaction networks specifically for AD+P and schizophrenia based on these genetic variations and genes. Network efficiency, which measures the signal transformation within the network, was calculated to characterize the topological structures of these two networks. The efficiency of antipsychotics in the two networks were calculated. Pathway enrichment analysis was used to identify pathways exclusively involved in AD+P.

Totally 1,135 and 2,085 genes were identified as related to AD+P and schizophrenia, respectively, with only 115 genes shared. Antipsychotics showed a significantly lower efficiency in AD+P than in schizophrenia (P<0.001). Several pathways (G Beta Gamma Signaling, IL-22 Signaling, etc.) were identified exclusively in AD+P rather than in schizophrenia and may be associated with the decreased efficacy of antipsychotics.

Psychotic symptoms in AD and schizophrenia may be caused by distinct mechanisms which result in a decreased efficacy of antipsychotics on AD+P.
Authors/Disclosures
Peihao Fan, MBBS (School of Pharmacy, University of Pittsburgh)
PRESENTER 		Mr. Fan has nothing to disclose.
Robert A. Sweet Robert A. Sweet has nothing to disclose.
No disclosure on file