BACE1 Physiological Functions May Limit Its Use as Therapeutic Target for Alzheimer’s Disease

Following my last post about potential treatments for Alzheimer’s, I found an article by Barão, et al. about inhibiting another pathway to prevent the disease. A certain cleaving enzyme, known as BACE1, is required for the body to produce the amyloid-beta peptide, which is  necessary for the pathogenesis of Alzheimer’s Disease. The article presents that although inhibition of BACE1 could be used to treat or even cure the disorder, there is still much to be known about how the enzyme, and ones similar to it, work. The article discusses the last three years of discovered information about BACE1.

Although this article was a little heavy and tough to digest, I still found it to be somewhat interesting. It was amazing to see how far research had taken us in the last three years and it makes me hopeful that there may be more and more treatments or preventions for Alzheimer’s as time goes on. As a future pharmacist, preventing a diseases like Alzheimer’s will lead to great health outcomes, not just because the disease can be treated, but because things like loss of memory and motor function will not affect how a patient takes their medications. What do you think about this kind of research? Do you think it matters to a pharmacist?

Link to the article

Barão, Soraia, Diederik Moechars, Stefan F. Lichtenthaler, and Bart De Strooper. “BACE1 Physiological Functions May Limit Its Use as Therapeutic Target for Alzheimer’s Disease.” Trends in Neurosciences39.3 (2016): 158-69. Web.

Pharmacological targeting of CSF1R inhibits microglial proliferation and prevents the progression of Alzheimer’s-like pathology

Olmos-Alonso, Schetters, et al. recently conducted a study to research potential ways to prevent patients from developing Alzheimer’s Disease (AD). Specifically they wanted to see the effect that activation of the colony-stimulating factor 1 receptor (CSF1R) had on progression of the disease, since the CSF1R promotes the creation and activation of microglial cells, which can lead to many neurodegenerative disorders, such as AD. The study provided some early evidence that inhibition of CSF1R could be a potential treatment to prevent the progression of AD.

Although this study only used mice, I think it was interesting to see that they had potentially found a pathway to interrupt in order to prevent, or at least slow, the progression of Alzheimer’s. As some one who has Alzheimer’s in his family history, it at least eases my fears when I see that steps are being made towards treatments for the disorder. I do realize that a lot more work and research needs to be done into this pathway and how exactly a medication could treat it, but I still found this article to be noteworthy. What do you think?

Link to the article

Olmos-Alonso, Adrian, Sjoerd T. T. Schetters, Sarmi Sri, Katharine Askew, Renzo Mancuso, Mariana Vargas-Caballero, Christian Holscher, V. Hugh Perry, and Diego Gomez-Nicola. “Pharmacological Targeting of CSF1R Inhibits Microglial Proliferation and Prevents the Progression of Alzheimer’s-like Pathology.” Brain 139.3 (2016): 891-907. Web.

NO2 Inhalation Promotes Alzheimer’s Disease-Like Progression

A study was performed on C57BL/6J and APP/PSI mice to determine how NO2 affected neuronal function. This was done because air pollution has been connected with higher risks of cognitive impairment and neurodegenerative diseases. NO2 is a typical primary air pollutant and a contributor to aerosols. In this study, the mice were exposed to NO2 inhalation. This showed that this inhalation led to spatial learning and memory deterioration, aggravated amyloid  β42 (Aβ42) accumulation, and induced pathological abnormalities and cognitive defects associated with Alzheimer’s disease.

The data showed that cyclooxygenase-2 (COX-2)-mediated arachidonic acid metabolism of prostaglandin E2 (PGE2) played a key role in these results. It was found that increasing endocannabinoid 2-arachidonoylglycerol (2-AG) by inhibiting monoacylglycerol lipase (MAGL) prevented the production of PGE2, Aβ42 accumulation, and neurodegeneration. This showed that MAGL inhibitors could be a potential drug therapy for treating NO2-induced cognitive impairment.

The questions I have are how would we know when to recommend this therapy and what are the side effects of it? Could it be used to treat Alzheimer’s Disease? Is this even a safe method for treating impaired neuronal function?

Sci Rep. 2016 Mar 01;doi:10.1038/srep22429

http://www.nature.com/articles/srep22429

 

Using Medication Adherence as an Indicator of Cognitive Dysfunction Among the Elderly

Anyone who has been required to take a medication on a daily basis can attest to the fact that it is very easy to forget or skip a dose. Imagine having to remember to take 6 or 7 medications everyday at different times of the day. This undoubtedly requires a certain level of cognitive ability and a clear mind to be able to organize all of one’s medications and to proceed to remember to take them. While one can usually stay adherent to his medications if some sort of system is set up for him, a decline in cognitive function and the development of dementia may nullify all efforts to keep track of and remain adherent to his medications.

This study assesses the possibility of using medication adherence as an indicator of the development of cognitive dysfunction in elderly individuals. This was a retrospective cross-sectional study, which examined 3351 Japanese patients with a mean age of 78.9 years old. Participants completed a comprehensive cognitive function test and got their medication use checked by clinical pharmacists. The Lawton’s instrumental activities of daily living (IADLs) scale assessed participants’ abilities to carry out self-care tasks in 8 categories such as the ability to use a telephone, transportation use, ability to handle finances, and responsibility for own medications. The Barthel Index score assessed another 10 self-care categories and the MMSE (Mini-Mental State Examination) measured participants’ orientation in time and space, attention, memory, language, and constructive skills.

The results of this study demonstrated that those in the early stage of cognitive failure were unable to perform activities of daily living (ADLs) in the “shopping” and “responsibility for own medications” categories. Moreover, the data from this study showed that there was a significant association between poor medication adherence and many other factors such as the use of Alzheimer’s disease medication, advanced age, and low Barthel index scores. Of the 3351 patients in this study, 2753 had some sort of cognitive dysfunction, and almost all patients diagnosed with dementia demonstrated a lower adherence to their medications in this study.

This study reveals that IADL scores are an effective method of predicting cognitive dysfunction in elderly individuals. Medication adherence and the development of dementia are both extremely important issues that require immediate attention. Pharmacists can play a huge role in caring for the elderly by providing screenings to measure for cognitive dysfunction and, in doing so, monitoring the elderly’s medication adherence as well.

Mizokami F, Mase H, Kinoshita T, et al. Adherence to Medication Regimens is an Effective Indicator of Cognitive Dysfunction in Elderly Individuals. Am J Alzheimers Dis Other Demen. 2016; 31(2):132-36

http://aja.sagepub.com.pitt.idm.oclc.org/content/31/2/132.full.pdf+html