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Schizophrenia breakthrough and question re connection to dementia
LDDaughter
Posted: Sunday, January 31, 2016 5:14 PM
Joined: 12/22/2011
Posts: 1065


I'd be interested in getting your thoughts about this new breakthrough discovery regarding the genetic pathways associated w schizophrenia and how you think it may or may not be related to cases of dementia where the individual has hallucinations and other behaviors similar to schizophrenia. From my mother's own issues with psychosis with her dementia I've been curious about this.  I am encouraged by this article and although I know these are different conditions I do think that research on other neurological/brain issues like this, Parkinson's and ALS are fascinating and I hope might have applications for dementia and Alzheimers.  For example, I recall reading awhile ago that research is being done with s with deep brain electrical? stimulation for Parkinson's and they may have tried this successfully on people with Alzheimers. 

http://www.sciencedaily.com/releases/2016/01/160127141400.htm


Lane Simonian
Posted: Sunday, January 31, 2016 9:53 PM
Joined: 12/12/2011
Posts: 4986


One of the most difficult questions in Alzheimer's disease is why do some people develop hallucinations and others don't.  I have found a few clues over the years but nothing definitive.


 2004 Summer;16(3):261-76.

The role of norepinephrine in the behavioral and psychological symptoms of dementia.

Abstract

The behavioral and psychological symptoms of dementia (BPSD) are common serious problems that are a major contributor to caregiver burden. Despite their significance, the underlying neurobiology of these disturbances is still unclear. This review examines the role of norepinephrine (NE) on BPSD, including depression, aggression, agitation and psychosis. A number of lines of evidence suggest that NE dysfunction leading to BPSD may result from increased NE activity and/or hypersensitive adrenoreceptors compensating for loss of NE neurons with progression of Alzheimer's disease (AD). With greater appreciation of the underlying neurobiology of behavioral and psychological symptoms of dementia (BPSD) more effective, rational, targeted pharmacotherapy will hopefully emerge.

 

An excess of norepinephrine has also been linked to schizophrenia.


One cause of high levels of norepinephrine found in schizophrenia and Alzheimer's disease is excessive levels of glutamate via NMDA receptors and caused by oxidative stress.


NMDA Receptor Activity in Neuropsychiatric Disorders

N-Methyl-d-aspartate (NMDA) receptors play a variety of physiologic roles and their proper signaling is essential for cellular homeostasis. Any disruption in this pathway, leading to either enhanced or decreased activity, may result in the manifestation of neuropsychiatric pathologies such as schizophrenia, mood disorders, substance induced psychosis, Huntington’s disease, Alzheimer’s disease, and neuropsychiatric systemic lupus erythematosus. Here, we explore the notion that the overlap in activity of at least one biochemical pathway, the NMDA receptor pathway, may be the link to understanding the overlap in psychotic symptoms between diseases. This review intends to present a broad overview of those neuropsychiatric disorders for which alternations in NMDA receptor activity is prominent thus suggesting that continued direction of pharmaceutical intervention to this pathway may present a viable option for managing symptoms.

A precursor to NMDA receptor activation is a molecule called myo-inositol.  It is often a precursor to Alzheimer's disease in people with Down syndrome or in mild cognitive impairment.  In many people with the disease it decreases, but where it remains high due to direct activation of g proteins [by aluminium fluoride, sodium fluoride, nicotine, stress perhaps, and probably other factors] behavioral problems appear to result.

More recently, a group in Japan correlated elevated brain myoinositol with behavioral and psychological problems in AD patients.

Compounds that either prevent the buildup, bind to, eliminate, or block the conversion of myo-inositol include ferulic acid, THC in medicinal marijuana, estrogen, and glucoronolactones--have all shown some promise in helping with behavioral and pyshcological problems in Alzheimer's disease.

I just looked up the complement component C4 receptor alluded to in the article also known as Integrin alphaXbeta2.

Here is its relationship to Alzheimer's disease: 

Integrins regulate Src kinases that are known to phosphorylate NMDA receptors.

Inhibition of Src kinase activity attenuates amyloid associated microgliosis in a murine model of Alzheimer's disease

[the problem, though, is not with amyloid but with zinc that contributes to the formation of amyloid].


Genetic or "environmental" (due to bacterial or viral diseases) overexpression of integrins may be a problem in several neurodegenerative diseases as well as schizophrenia.

 


Lane Simonian
Posted: Sunday, January 31, 2016 9:55 PM
Joined: 12/12/2011
Posts: 4986


I forgot to mention there has been some progress with deep brain stimulation for Alzheimer's disease.  Eden maybe able to provide more details.
Lane Simonian
Posted: Sunday, January 31, 2016 10:18 PM
Joined: 12/12/2011
Posts: 4986


Well this is interesting:


Compared to deep brain electrical stimulation, which has been applied to treating pathological brain diseases, little work has been done on the effect of deep brain light stimulation. A fiber-coupled laser stimulator at 840 nm wavelength and 130 Hz pulse repetition rate is developed in this work for deep brain light stimulation in a rat model. Concentration changes in glutamate and dopamine in the striatum are observed using a microdialysis probe when the subthalamic nucleus (STN) is stimulated at various optical power levels. Experimental results show that light stimulation causes the concentration of glutamate to decrease while that of dopamine is increased. This suggests that deep brain light stimulation of the STN is a promising therapeutic strategy for dopamine-related diseases such as Parkinson’s disease. The stimulator developed for this work is useful for deep brain light stimulation in biomedical research.

This should also help for Alzheimer's disease.