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Tau buildup in brain tied to psychosis, more rapid decline in Alzheimer’s disease

Translational Psychiatry
Reuters Health - 11/03/2022 - Increased concentrations of the tau protein in the brain's frontal, medial and occipital cortices are associated with psychosis and more rapid cognitive and functional decline in Alzheimer's disease (AD) patients, an imaging study shows. 

Dr. Jeremy Koppel of the Feinstein Institutes for Medical Research in Manhasset, New York, told Reuters Health by email, "Psychosis in AD may represent a unique kind of tauopathy, similar... to the way chronic traumatic encephalopathy is a unique tauopathy - different under the microscope from Alzheimer's disease." 

"Studies need to look closer at distinguishing this syndrome from non-psychotic AD so that treatments can be developed," he said. 

Tau positron emission tomography (PET) enables researchers to evaluate and correlate disease pathology with symptomatology using (18F)-AV1451, a PET ligand with high affinity for insoluble paired-helical filaments of hyperphosphorylated tau, Dr. Koppel and colleagues explain in Translational Psychiatry. 

The researchers identified 17 participants in the Alzheimer's disease neuroimaging initiative (ADNI) who had (18F)-AV1451 imaging at baseline and became psychotic over the course of the study and matched them for gender, age, and education to 50 individuals who did not become psychotic. 

They compared baseline (18F)-AV1451 retention, and cognitive and functional baseline and longitudinal change, between those who became psychotic and those who did not. 

The results suggested that increases in tau pathology in frontal, medial temporal, and occipital cortices, visualized with 18F)-AV1451 binding, are associated with psychosis and a more rapid cognitive and functional decline. 

Dr. Koppel said, "The next step in our research is to begin to recruit patients to participate in a tau PET imaging study so that we can better understand - in relationship to the full range of psychotic symptoms - where exactly in the brain the tau builds up. This will help us to develop therapies." 

"The biggest challenge is finding participants willing to volunteer to be a in a research study," he noted. "We are at a point with the science where we know that what we are trying to do is scientifically feasible; we just need patients and their families to want to help make the future better for other people suffering with this terrible disease, and to volunteer to get a PET scan." 

Dr. Gwenn Smith, Director, Division of Geriatric Psychiatry and Neuropsychiatry at Johns Hopkins University School of Medicine in Baltimore commented on the study in an email to Reuters Health. "In vivo molecular imaging such as PET can provide unique insights into the role of proteins and neurotransmitters in the development of psychosis in AD. The results are promising." 

However, she noted, "As the investigators point out, the sample size was small and medication use was not controlled. Further studies are needed to study the longitudinal course of tau in relation to the development of psychosis and to evaluate the dimensions of psychosis in further detail (e.g., delusion, hallucinations)." 

"Future studies are needed to understand the mechanisms that produce greater tau levels in AD patients with psychotic symptoms and also the synaptic changes that are associated with higher tau (e.g., degeneration of dopamine and serotonin neurons)," she said. "Such information will inform the development of more effective treatments for psychosis in AD." 

"Higher tau may also be associated with greater sensitivity to the side effects of antipsychotic medications," she added. "The greater neuropathology and cognitive deficits associated with psychosis in AD support careful monitoring in the use of (these) medications." 

SOURCE: https://go.nature.com/3vZAD81  Translational Psychiatry, online February 26, 2022. 

By Marilynn Larkin 

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