Fixing the Alzheimer’s Gene

The gene APOE has been heavily researched in connection with causing Alzheimer’s, with the latest research suggesting that the gene can be “fixed” through the administration of a lab-engineered APOE4 to the faulty gene, resulting in structural changes that make the APOE4 gene behave more like the APOE3 gene, the inoffensive gene.

Applying the modified APOE4 gene to human neurons corrected the defects, restoring normal cell function, prolonging cell life and erasing the signs of the disease.

If someone has one copy of the APOE4 gene, their risk of developing Alzheimer’s increases three fold and if they have two copies their risk is increased twelve fold. The role of APOE in the body is to provide instructions for synthesising proteins and in combination with fats, liproprotein complexes are formed which are used to transport cholesterol through the blood stream.

The E4 variant has been strongly linked to the build up of beta-amyloid plaques in the brain- however this was only observed after the gene was studied in human cells in the lab- in mice, there was no beta-amyloid build up in the neurons. This is often a large stumbling block in developing effective Alzheimer’s treatments- new drugs model perfectly in mice, however in humans there are discrepancies in terms of their efficacy. This new research represents a new frontier in developing effective treatments.

1. [Accessed 21/05/2018]

Halting Alzheimer’s Disease with SERCA activator

Research published by Purdue University indicates the possibility of slowing down or even halting Alzheimer’s. The research presents the SERCA activator as reducing cellular stress and preventing cell loss through the correction of calcium ions within the cell- this signifies a new frontier in therapeutic strategies for targeting neurodegenrative drug development.

Typically, brain cell loss occurs due to an imbalance in calcium ions, the research conducted aims to directly rectify this imbalance. The researchers developed molecules that target calcium handling proteins- in this case SERCA. Researcher’s focused on the role of the SERCA activator in neurodegenrative disorders. The aim of this study was primarily geared towards developing a drug that protects against cellular injury.

The evidence for the positive on Alzheimer’s is promising, the SERCA activator allowed for a 60% reduction in beta-amyloid plaques. The SERCA activator can also reverse apoptosis of cells, essentially reviving them from death. This is significant as the prevention of apoptosis can directly prevent neurodegeneration. This development is not only significant for treating Alzheimer’s but also other neurodegenrative diseases such as Parkinson’s and ALS.


Image taken from original study (2) demonstrating how the SERCA Activator may work. 

1. – Original Article

2. – Original Study

Charles Bonnet Syndrome

After watching Oliver Sacks’ TED talk, “What Hallucination Reveals About Our Minds”, I was intrigued by a dementia patient who was experiencing hallucinations after going blind through macular degeneration. Sacks had concluded that she was suffering from Charles Bonnet Syndrome, or also called Visual Release Hallucinations. This post aims to give an outline of the syndrome, and explore treatments and causes.

Charles Bonnet Syndrome (CBS) is characterised as a type of psychophysical visual disturbance and sufferers are blind or severely visually impaired and experience intricate visual hallucinations. A characteristic of these hallucinations is the that they appear “lilliputian”, i.e. they are smaller than usual. Cartoons are typical hallucinations, as Sacks’ patient commonly experienced. The significant part of CBS is that the sufferer’s are aware that the hallucinations are not real.

The prevalence of CBS was explored in an Australian Study which found that amongst adults over 65, 17.5% experienced these hallucinations. However the incidence may be higher as sufferer’s may be fearful of reporting the hallucinations for fear of being labelled mentally ill.

The syndrome can be developed after damage to the bilateral optic nerve occurs through methyl alcohol poisoning. Macular degeneration combined with restriction of the visual field after glaucoma can also predispose CBS. Diabetes-related eye conditions and cataracts can also lead to visual hallucinations. The hallucinations experienced in CBS can be heightened through intense emotional distress such as grief, or depression, sensory deprivation, strokes and impaired cognitive abilities.

The hallucinations occur as a result of the brain reacting to losing sight, the brain reacts to visual loss by producing images that had previously been seen, as it is no longer receiving any visual input.

There are not express treatments for CBS, however it has been observed that after the patients are aware that the hallucinations are not part of a mental disorder, but a reaction to loss of sight, the hallucinations become less frequent. It is believed that no treatment is required due to the fact that the hallucinations are believed not to be permanent and will eventually fade away on their own.

However, it has been found that drugs used to treat Parkinson’s, dementia and epilepsy have been found to alleviate the hallucinations- but it must be known that these medications have side-effects, and it is also possible that these medications intensify the hallucinations.


Exploration in the aetiology of Autism Spectrum Disorder

A common question associated with Autism Spectrum Disorder (ASD), is what causes it? The precise cause is unknown, although there is significant research into the aetiology of the disorder that provides some insight.

ASD is believed to be caused by multiple influences such as environmental, biological and genetic factors. The influences of these factors may explain the spectrum of behaviour observed in people with ASD. ASD may be associated with various conditions affecting brain development such as maternal rubella (including other viral diseases of the central nervous system) or post-encephalitic neuroinflammation but this link remains unclear. Some research has hinted at the possibility of ASD being caused by fragile X syndrome, encephalitis and untreated phenylketonuria.

Fragile X syndrome is a genetic condition which causes developmental problems, including ASD. It affects males more severely than females, and affected persons characteristically have delayed speech and language development. One third of females affected are intellectually disabled with most males having moderate intellectual disability. About one-third of people with fragile X syndrome have features of ASD. Fragile X syndrome is the most prevalent known single gene cause of ASD.

Autoimmune encephalitis is where the immune system attacks the brain- impairing its function. Research has suggested that children with ASD have a brain pathology indicating ongoing neuroinflammation or encephalitis. It is estimated that around 69% of children with ASD have neuroinflammation- however children who are diagnosed with ASD are not typically tested for encephalitis. This means that if a child has developed ASD as a result of encephalitis, they could receive treatment that reduces the deficits of ASD.

Phenylketonuria is a fault in the metabolism that leads to the decrease in metabolic activity involving the amino acid phenylalanine. It is an inherited disorder and is due to the mutation in the PAH gene which subsequently influences the levels of the enzyme phenylalaline hydroxylase- significantly lowering them. Left untreated, it can lead to intellectual disability and possibly autism.

Maternal rubella is associated with ASD, it was found that children with ASD had an “altered immune response to rubella vaccination” (5), this suggested that they had already been affected by rubella. With Chess (1971) finding that children with congenital rubella had an increased incidence of ASD. It was suggested from this that congenital rubella of the central nervous system could produce the complex and severe social deficits of ASD.

This is only small insight into the possible aetiology of autism spectrum disorder, however current research is providing more evidence for the possible causes of ASD.

1. [Accessed 03/05/2018]
2. [Accessed 03/05/2018]
3. Kern, Janet K., et al. “Relevance of Neuroinflammation and Encephalitis in Autism.” Frontiers in Cellular Neuroscience, vol. 9, 2016, doi:10.3389/fncel.2015.00519.