Alzheimer’s disease (AD) is one of the most fearsome and recalcitrant scourges of neurology. We think we know a lot about it; after all it has been a quite a while since Alois Alzheimer described amyloid plaques and neurofibrillary tangles in his index patient, Frau Deter. But the more neuroscientists study the disease, the murkier the field looks. For example, we are still not quite sure what the plaques and tangles really signify; for all we know, they may just be innocent bystanders, powerless by-products of a neurodegenerative process that defies understanding. We have accumulated an endlessly long list of AD risk factors, but we have singularly been unable to point a finger at the cause of AD.
This elusive void may however be a void no longer, if what superficially appears to be an outlandish theory turns out to be correct. And the theory is that AD is caused by infection! Just take a deep breathe, and allow yourself the space to make a giant leap of imagination. My attention was first drawn to the infective hypothesis of AD by a headline in Scientific American screaming Controversial New Push to Tie Microbes to Alzheimer’s Disease. The obvious key word here of course is controversial: is it possible that AD, this quintessential neurodegenerative disease, is…just another chronic infection?
To find the original source of the story, the trail of bread crumbs led to an editorial published in the Journal of Alzheimer’s Disease in 2016, plainly titled Microbes and Alzheimer’s Disease. But this is not a run-of-the-mill editorial at all because it was written by 33 senior scientists and clinicians from a dozen countries. And their reason for an alternative theory of AD is simple: amyloid, the long-suspected culprit for decades, has failed to live up to its billing. They point out that amyloid exists harmlessly in the brains of many older people who never go on to develop dementia. They also cite studies which demonstrate that treating amyloid, by immunological means, does not improve the state of people suffering from AD. Amyloid, in other words, is not such a bad guy after all. But all the while we have been setting traps to ensnare it, the microbial villains have been running amok, having a field day.
But why should microbes succeed where amyloid, the ubiquitous protein, has woefully failed? The editorial gave 8 good reasons to argue that the infection theory is better than the amyloid hypothesis. One reason is that the brains of people with AD are often riddled with inflammation, a characteristic feature of infections. Another reason is the observation that AD can be transferred to primates when they are inoculated with the brain tissue of someone with AD.
And the culprit with the most number of index fingers pointing at it is herpes simplex virus type 1 (HSV1). The editorial tells us that there have been about 100 publications, by different groups, demonstrating that HSV1 is a ‘major factor‘ in the causation of AD. Some of these studies have shown that people with AD have immunological signs of significant HSV infection in their blood. The editorial goes further to review the possible mechanisms by which HSV1 may cause AD; one of these is the possibility that the virus lowers the risk of AD in people who possess the APOE ɛ4 allele genetic liability.
Just when you are getting your head round the idea, the infection theory takes a very sinister turn. And this relates to the perversemodus operandi of the microbes. The authors tell us that the microbes first gain access to the brains of their victims when they (the victims) were much younger. Like sleeper cells in their ghoulish crypts, the microbes hibernate, biding their time until their victims get older, and their immunity declines. The microbes then awaken, and like malevolent zombies, set out to wreak gory mayhem and cataclysmic destruction. And they do this either by causing direct damage to the brain, or indirectly by inducing inflammation.
You can now descend form your giant imaginative leap and start to wonder: if AD is indeed caused by microbes, what can we do about it? ‘Tis time for some down-to-earth deep thinking.
Traumatic brain injury (TBI) is simply disheartening. It is particularly devastating because it usually affects young people in their prime, with the consequent personal, social, and economic consequences. This blog has previously touched a little on TBI with the post titled Will Smith and chronic traumatic encephalopathy?This was a light-hearted take on concussion in sports, but traumatic brain injury is nothing but a serious burden. So what are the big brains in white coats doing to take down this colossus? Quite a lot it seems. Here, for a taster, are 9 promising advances in the management of traumatic brain injury.
An amyloid PET imaging study by Gregory Scott and colleagues, published in the journal Neurology, reported a rather surprising link between the pathology seen in long-term survivors of traumatic brain injury, with the pathology seen in Alzheimers disease (AD). In both conditions, there is an increased burden of β-amyloid (Aβ) in the brain, produced by damage to the nerve axons. The paper, titled Amyloid pathology and axonal injury after brain trauma, however notes that the pattern of Aβ deposition in TBI can be distinguished from the one seen in AD. The big question this finding raises is, does TBI eventually result in AD? The answer remains unclear, and this is discussed in the accompanying editorial titled Amyloid plaques in TBI.
The ideal biomarker for any disorder is one which is easy to detect, such as a simple blood test. A headline that screams Blood test may offer new way to detect concussionsis therefore bound to attract attention. The benefits of such a test would be legion, especially if the test can reduce the requirement for CT scans which carry the risks of radiation exposure. This is where glial fibrillary acidic protein (GFAP) may be promising. The research is published in the journal, Academic Research Medicine, with a rather convoluted title, Performance of Glial Fibrillary Acidic Protein in Detecting Traumatic Intracranial Lesions on Computed Tomography in Children and Youth With Mild Head Trauma. The premise of the paper is the fact that GFAP is released into the blood stream from the glial cells of the brain soon after brain injury. What the authors therefore did was to take blood samples within 6 hours of TBI in children. And they demonstrated that GFAP levels are significantly higher following head injury, compared to injuries elsewhere in the body. This sounds exciting, but we have to wait and see where it takes us.
Brain Scars Detected in Concussionsis the attention-grabbing headline for this one, published in MIT Technology Review. Follow the trail and it leads to the actual scientific paper in the journal Radiology, with a fairly straight-forward title, Findings from Structural MR Imaging in Military Traumatic Brain InjuryThe authors studied >800 subjects in what is the largest trial of traumatic brain injury in the military. Using high resolution 3T brain magnetic resonance imaging (MRI), they demonstrated that even what is reported as mild brain injury leaves its marks on the brain, usually in the form of white matter hyperintense lesions and pituitary abnormalities. It simply goes to show that nothing is mild when it comes to the brain, the most complex entity in the universe.
Current technologies which monitor patients with traumatic brain injury are, to say the least, cumbersome and very invasive. Imagine if all the tubes and wires could be replaced with microsensors, smaller than grains of rice, implanted in the brain. These would enable close monitoring of critical indices such as temperature and intracranialpressure. And imagine that these tiny sensors just dissolve away when they have done their job, leaving no damage. Now imagine that all this is reality. I came across this one from a CBS News piece titled Tiny implanted sensors monitor brain injuries, then dissolve away. Don’t scoff yet, it is grounded in a scientific paper published in the prestigious journal, Nature, under the title Bioresorbable silicon electronic sensors for the brain. But don’t get too exited yet, this is currently only being trialled in mice.
What if the inflammation that is set off following traumatic brain injury could be stopped in its tracks? Then a lot of the damage from brain injury could be avoided. Is there a drug that could do this? Well, it seems there is, and it is the humble blood pressure drug Telmisartan. This one came to my attention in Medical News Today, in a piece titled Hypertension drug reduces inflammation from traumatic brain injury. Telmisartan seemingly blocks the production of a pro-inflammatory protein in the liver. By doing this, Telmisartan may effectively mitigate brain damage, but only if it is administered very early after traumatic brain injury. The original paper is published in the prestigious journal, Brain, and it is titled Neurorestoration after traumatic brain injury through angiotensin II receptor blockage. Again, don’t get too warm and fuzzy about this yet; so far, only mice have seen the benefits.
Fatigue is a major long-term consequence of traumatic brain injury, impairing the quality of life of affected subjects in a very frustrating way. It therefore goes without saying, (even if it actually has to be said), that any intervention that alleviates the lethargy of TBI will be energising news. And an intervention seems to be looming in the horizon! Researchers writing in the journal, Acta Neurologica Scandinavica, have reported that Methylphenidate significantly improved fatigue in the 20 subjects they studied. Published under the title Long-term treatment with methylphenidate for fatigue after traumatic brain injury, the study is rather small, not enough to make us start dancing the jig yet. The authors have rightly called for larger randomized trials to corroborate their findings, and we are all waiting with bated breaths.
Many survivors of traumatic brain injury are left with behavioural disturbances which are baffling to the victim, and challenging to their families. Unfortunately, many of the drugs used to treat these behaviours are not effective. This is where some brilliant minds come in, with the idea of stimulating blood stem cell production to enhance behavioural recovery. I am not clear what inspired this idea, but the idea has inspired the paper titled Granulocyte colony-stimulating factor promotes behavioral recovery in a mouse model of traumatic brain injury. The authors report that the administration of G‐CSF for 3 days after mild TBI improved the performance of mice in a water maze…within 2 weeks. As the water maze is a test of learning and memory, and not of behaviour, I can only imagine the authors thought-surely only well-behaved mice will bother to take the test. It is however fascinating that G‐CSF treatment actually seems to fix brain damage in TBI, and it does so by stimulating astrocytosis and microgliosis, increasing the expression of neurotrophic factors, and generating new neurons in the hippocampus“. The promise, if translated to humans, should therefore go way beyond water mazes, but we have to wait and see.
The idea behind using Etanercept to promote recovery from brain injury sound logical. A paper published in the journal, Clinical Drug Investigation, explains that brain injury sets off a chronic lingering inflammation which is driven by tumour necrosis factor (TNF). A TNF inhibitor will therefore be aptly placed to stop the inflammation. What better TNF inhibitor than Eternacept to try out, and what better way to deliver it than directly into the nervous system. And this is what the authors of the paper, titled Immediate neurological recovery following perispinal etanercept years after brain injury, did. And based on their findings, they made some very powerful claims: “a single dose of perispinal etanercept produced an immediate, profound, and sustained improvement in expressive aphasia, speech apraxia, and left hemiparesis in a patient with chronic, intractable, debilitating neurological dysfunction present for more than 3 years after acute brain injury”. A single patient, mind you. Not that I am sceptical by nature, but a larger study confirming this will be very reassuring.
And finally, that elusive holy grail of neurological therapeutics, neuroprotection. Well, does it exist? A review of the subject published in the journal, International Journal of Molecular Sciences, paints a rather gloomy picture of the current state of play. Titled Neuroprotective Strategies After Traumatic Brain Injury, it said “despite strong experimental data, more than 30 clinical trials of neuroprotection in TBI patients have failed“. But all is not lost. The authors promise that “recent changes in experimental approach and advances in clinical trial methodology have raised the potential for successful clinical translation”. Another review article, this time in the journal Critical Care, doesn’t offer any more cheery news about the current state of affairs when it says that the “use of these potential interventions in human randomized controlled studies has generally given disappointing results”. But the review, titled Neuroprotection in acute brain injury: an up-to-date review, goes through promising new strategies for neuroprotection following brain injury: these include hyperbaric oxygen, sex hormones, volatile anaesthetic agents, and mesenchymal stromal cells. The authors conclude on a positive note: “despite all the disappointments, there are many new therapeutic possibilities still to be explored and tested”.
The Neurology Lounge strives hard to keep to the straight and narrow path of clinical neurology. But every now and then it takes a peek at what is happening at the cutting edge of neuroscience. And what can be more cutting edge then biomarkers, with their promise of simplifying disease identification, making prompt and accurate diagnosis an effortless task.
The quintessential biomarker however remains as elusive as quicksilver. Not that one could tell, going by the rate biomarkers are being spun from the neuroscience mills. Biomarkers are the buzz in many neurological fields, from brain tumours to multiple sclerosis (MS), from Alzheimer’s disease (AD) to Huntington’s disease (HD).
The proliferation of contending biomarkers is however probably highest in the field of motor neurone disease (MND). Is there a holy grail out there to enable the rapid and accurate diagnosis of this relentlessly progressive disease? There is clearly no dearth of substances jostling for prime position in the promised land of MND biomarkers. Below is a shortlist of potential MND CSF biomarkers; just click on any to go to the source!
Neurology embodies some of the most dreadful diseases known to man. Every neurological disorder is disheartening, each characterised by unique frustrations for patients and their families. It is difficult to quantify the distress and misery these afflictions impose on their victims, and even harder to appreciate the despair and anguish they evoke in those who care for them.
It is clearly hard to compare the impact of different neurological diseases. Some neurological disorders however stand out because of the consternation their names evoke, and the terror that follows in their wake. These diseases come with unimaginable physical and psychological burdens, and crushing demands on human and material resources. They impose either a debilitating morbidity, or a hasty mortality.
The nervous system ailments in the list below pose exacting therapeutic challenges, resistant as they are to all attempts at treatment or cure. This list sets out to emphasise the urgency for neuroscience to find a remedy for each of them, but it does not intend to belittle the horror of the disorders omitted from it. The choice of the number 13 is, sadly, self-evident. Here then are the top 13 most dreadful neurological disorders…all with gold links to the associations helping to defeat them.
Ataxia, in lay terms, is incoordination. This typically manifests as an unsteady gait and clumsiness. Ataxia converts all activities of daily living into burdensome chores. Whilst many types of ataxia are preventable or reversible, primary ataxias are progressive and carry a dismal outlook. In this category are Spinocerebellar ataxia (SCA), Friedreich’s ataxia, and Ataxia telangiectasia. You may read more about ataxia in these previous blog posts:
Brain cancers hardly need any description. They are either primary, arising from the brain cells, or metastatic, spreading to the brain from other organs. Some primary brain cancers, such as meningiomas and pituitary tumours, are, relatively, treatable. Many others are unfortunately ominously malignant. The most dreadful in this category is surely the spine-chilling glioblastoma multiforme. You may check out these previous blog posts for more on these tumuors:
Peripheralneuropathy is ubiquitous in the neurology clinic. Neuropathy may result from reversible situations such as overindulgence in alcohol, uncontrolled diabetes, or Vitamin B12 deficiency. Neuropathy is often just a minor inconvenience when it manifests with sensory symptoms such as tingling and numbness. It may however be debilitating when it presents as limb paralysis, or complicated by major skeletal deformities. At the severe end of the spectrum of neuropathy are the hereditary forms such as CharcotMarie Tooth disease (CMT) and Familialamyloid polyneuropathy. Read more in these blog posts:
CJD is the most iconic of the prion diseases. These disorders are as horrendous as they are enigmatic, defying categorisation as either infections or neurodegenerative diseases. More puzzling is their ability to be either hereditary and acquired. CJD exists in the classic or variant form, but both share a relentlessly rapid course, and a uniformly fatal end. You may read more in these previous blog posts titled:
Dystonia marks its presence by distressing movements and painful postures. At its most benign, dystonia is only a twitch of the eyelid (blepharospasm) or a flicker of one side of the face (hemifacial spasm). At the extreme end, it produces continuous twisting and swirling motions, often defying all treatments. The causes of dystonia are legion, but the primary dystonias stand out by their hereditary transmission and marked severity. Read more on dystonia in these blog posts:
Huntington’sdisease is an iconic eponymous neurological disorder which is marked by the vicious triumvirate of chorea, dementia, and a positive family history. It is an awful condition, often driving its victims to suicide. It is a so-called trinucleotide repeat expansion disorder, implying that successive generations manifest the disease at an earlier age, and in more severe forms (genetic anticipation). You may read more on HD in the previous blog post titled:
Also known as Amyotrophiclateral sclerosis (ALS), MND is simply devastating. Recognising no anatomical boundaries, it ravages the central and peripheral nervous systems equally. MND creeps up on the neurones and causes early muscle twitching (fasciculations) and cramps. It then gradually devours the nerves resulting in muscle wasting, loss of speech, ineffectual breathing, and impaired swallowing. Our previous blog posts on MND are:
Multiple sclerosis is a very common disease, and gets more common the further away you get from the equator. It is the subject of intense research because of the devastation it foists on predominantly young people. Many drugs now ameliorate, and even seem to halt the progression of, relapsing remitting MS (RRMS). This is however not the case with primary progressive MS (PPMS) which, until the introduction of ocrelizumab, defied all treatments. There are many contenders vying for the cause of MS, but the reason nerves in the central nervous system inexplicably lose their myelin sheaths remains elusive. You may read more on MS in these blog posts:
Rabies, a rhabdovirus, is a zoonosis-it is transmitted to man by a wide range of animals such as dogs, bats, racoons, and skunks. It is the quintessential deadly neurological disease, popularised by the Steven King book and film, Cujo. Rabies manifests either as the encephalitic (furious) or the paralytic (dumb) forms. It wreaks havoc by causing irritability, hydrophobia (fear of water), excessive sweating, altered consciousness, and inevitably death. Whilst there are vaccines to protect against rabies, a cure has eluded neuroscientists. This blog is yet to do justice to rabies but it is, at least, listed in the post titled What are the most iconic neurologicaldisorders? But you could better by checking neurochecklists for details of the clinicalfeatures and management of rabies.
Nothing is quite as heart-wrenching as the sudden loss of body function that results from spinal cord trauma. This often causes paralysis of both legs (paraplegia), or all four limbs (quadriplegia). This life-changing disorder is often accompanied by loss of control over bowel and bladder functions, and complications such as bed sores and painful spasms. You may read about the heroic efforts to treat spinal cord injury in the blog posts titled:
Tetanus is an eminently preventable disease, now almost wiped out in developed countries by simple immunisation. It however continues its pillage and plunder in the developing world. It strikes young and old alike, often invading the body through innocuous wounds. Tetanus is caused by tetanospasmin and tetanolysin, the deadly toxins of the bacterium Clostridium tetani. The disease is classified as generalised, localised, cephalic, or neonatal tetanus. It is characterised by painful spasms which manifest as lockjaw (trismus), facial contortions (risus sardonicus), trunkal rigidity (opisthotonus), and vocal cord spasms (laryngospasm). The disease is awfully distressing and, when advanced, untreatable. It is a stain on the world that this avoidable disorder continuous to threaten a large number of its inhabitants. Check neurochecklists for more on the pathology,clinicalfeatures, and management of tetanus.
In the excellent book, The Innovators Prescription, the authors predict that precisionmedicinewill replace intuitive medicine, and diseases will be defined by their underlying metabolic mechanisms, and not by the organs they affect, or the symptoms they produce. Clayton Christensen and colleagues argue that this precise definition of diseases will lead to more effective treatments. But they also show that precision medicine will show that many different diseases actually share the same underlying metabolic derangements. Many disparate diseases will therefore turn out to be just mere manifestations of the same metabolic disease.
Why should Liraglutide work so well in both diabetes and Alzheimer’s, diseases with apparently different pathologies? The answer lies in insulin resistance, the underlying mechanism of type 2 of diabetes; there is now evidence that insulin resistance contributes to dementia. If this is the case, Liraglutide, by improving glucose metabolism, could potentially treat both diabetes and Alzheimer’s disease.
To explore this potential further, there is now a large multicentre trial exploring the real benefit of Liraglutide in Alzheimer’s disease. Titled Evaluating Liraglutide in Alzheimer’s Disease or ELAD, it is recruiting people with mild disease, aged between 50-85 years old, and who do not have diabetes. As they say, watch this space!
But why is a neurologist talking about seahorses. It’s all in the name. The Latin name for seahorse is hippocampus , derived from hippos for horse, and kampos for sea monster. Where biologists saw fish, the ancients saw monsters. And you really can’t blame them…take a closer look
Neurologists are passionate about the hippocampus for various reasons. In people with memory complaints, for example, hippocampal atrophy may predict the development of Alzheimer’s disease . A shrunken hippocampus is also seen in some forms of epilepsy. Neurologists thereforeendlessly harangue their neuroradiology colleagues to look closely at their patients’ brain MRI scans, and to tell them that the hippocampus is shrunken…even if it’s just a little bit smaller. Unfortunately for the neuroradiologists, the MRI scans do not come colour-coded as in the illustrative scan below.
This blog post is however about major depression, and not about epilepsy or dementia. Depression, that bad feeling we all feel every now and then is frustrating, but major depression is devastating. And we now know that it is accompanied by major alterations in the structure of the brain. And, yes, the changes are in the hippocampus. I got interested in this subject when I came across a piece in Neurology News reporting that people with depression have a smaller hippocampus.
The association of depression with hippocampal atrophy is however an old one. Proceedings of the National Academy of Science (PNAS) reviewed the relationship in an editorial from 2011 titledDepression, antidepressants, and the shrinking hippocampus. The author addressed the unresolved puzzle…which of the two came first. Reminiscent of the chicken and egg scenario, it is not clear if the hippocampal atrophy causes depression, or vice versa. To add to the puzzle, the paper conjectured the possibility of a third, unknown agent, causing both the depression and the small hippocampus.
This question was the focus of a meta-analysis published in Molecular Psychiatry this year. It reviewed the brain imaging data of 15 studies, involving about 1700 people with major depression. Titled Subcortical brain alterations in major depressive disorder, the authors confirmed the link between depression and hippocampal atrophy, and also showed that the shrinkage is worse in those who developed depression at an early age, and in those who have had frequent episodes of depression.
Does depression lead to hippocampal atrophy? The meta-analyses hinted so, but there were too many caveats for the authors to arrive at a definitive conclusion. They admit that more needs to be done to unravel depression….leaving the mystery of the shrinking seahorses to continue to another day.
Neurology is a broad specialty covering a staggering variety of diseases. Some neurological disorders are vanishingly rare, but many are household names, or at least vaguely familiar to most people. These are the diseases which define neurology. Here, in alphabetical order, is my list of the top 60 iconic neurological diseases, with links to previous blog posts where available.
The Neurology Lounge has a way to go to address all these diseases, but they are all fully covered in neurochecklists. In a future post, I will look at the rare end of the neurological spectrum and list the 75 strangest and most exotic neurological disorders.
Uncertainty and doubt abound in Neurology. There are many evidence-free areas where experts rub each other the wrong way. These controversies are big and occur in all neurology subspecialties. Controversy-busters have tried for about a decade to iron out these wrinkles on neurology’s face, but the unanswered questions remain. This is why there is a 10th World Congress of Controversies in Neurology (CONy) holding in Lisbon this year.
I want to assure you I have no conflict of interest to declare in this blog. My interest is to explore which questions have plagued this conference over the last 10 years to pick out the most controversial topics in neurology. To do this I reviewed all previous conference programs and focused on the items that were slated for debate. I looked for practical topics that have remained unresolved, or are just emerging. Here are my top controversial neurological questions:
Going through this list, I feel reassured that the experts differ in their answers to these questions? The acknowledgement of uncertainty allows us novices to avoid searching for non-existent black and white answers. It is however also unsettling that I thought some of these questions had been settled long ago. It goes to show that apparently established assumptions are not unshakable?
Do you have the definitive answers to resolve these controversies? Are there important controversies that are missing here? Please leave a comment
Alzheimer’s disease (AD) is scary. It is the most prevalent cause of dementia, and the name strikes terror, especially to those with a close family history of the condition. It is disturbing when a person loses the concept of ‘self’. It is devastating when parents fail to recognise their children.
Any progress in finding the cause or the cure for this neurodegenerative disease should therefore be celebrated. Following on my previous post, Alzheimer’s disease: a few curious things, here are my top10 breakthroughs giving hope for Alzheimer’s disease.
Based on a premise that high brain iron levels are related to the pathology in Alzheimer’s disease, researchers have looked at iron reducing therapies. This isn’t a new idea because an article in Lancet from 1991 was titled Intramuscular desferrioxamine in patients with Alzheimer’s disease. This study showed that the progression of Alzheimer’s disease could be slowed down by reducing the iron levels in the brain. New Scientist has brought this therapeutic strategy back into contention in its article titled Iron levels in brain predict when people will get Alzheimer’s. The article tantalisingly refers to a link between high iron levels and ApoE4, a gene associated with Alzheimer’s disease. Watch this space.
The idea of dampening the production of amyloid comes from the discovery of a new chemical pathway in the brain; I didn’t realise there were any more pathways left to discover! My ignorance was dispelled by this article in MNT titled A newly discovered molecular feedback process may protect the brain against Alzheimer’s. The article discusses WAVE-1, a protein which is central to a pathway involved in ß-amyloid production. How could scientists could suppress this pathway and improve the clearance of ß-amyloid? By somehow enhancing an inhibitory feedback loop thereby reducing WAVE-1 production. The scientific details are published in Nature Medicine titled APP intracellular domain–WAVE1 pathway reduces amyloid-β production.
It would be surprising if monoclonal antibodies did not crop up in this post, being the rage in many other diseases. The monoclonal antibody raising hopes in Alzheimer’s disease is Solanezumab. I came across this in Russia Today (yes…RT) in an article titled Alzheimer’s breakthrough? First ever drug found that may slow disease. ‘First ever’ is obviously hype, but there does seem to be some benefit of Solanezumab, even if this is restricted to those with early disease. The phase 3 trial of Solanezumab, called EXPEDITION 3, will study this effect further. More hope, less hype!
Microglia, the brain’s waste disposal cells, also play a key role in it’s immune system. In this way they protect the brain from damage by ß-amyloid. This immune function is however countered by EP2, a prostaglandin receptor protein found on the surface of the microglia. In other words EP2 functions to restrict the activity of the microglia. Researchers have now shown that the nuisance effect of EP2 could be blocked, as reported in an article titled Prostaglandin signaling suppresses beneficial microglial function in Alzheimer’s disease models, and published in Journal of Clinical Investigation. Enhancing the activity of microglia therefore raises hope for the treatment for Alzheimer’s disease… if it could be translated to humans.
What if we could boost the activity of cells that have not yet been affected by Alzheimer’s disease? An experimental drug called J147 might just do that. According to researchers, J147 is a neurotrophic drug which enhances nerve activity in mice. The research, appropriately published in the journal Aging, shows that J147 improves cognitive function in mice which have been modified to age fast. The article is titled A comprehensive multiomics approach toward understanding the relationship between aging and dementia. I personally prefer the headline in Neuroscience News which simply says Experimental Alzheimer’s Drug Slows Clock on Key Aspects of Aging. Too soon to speculate, but could we be talking age reversal here? Perhaps competition for klotho.
We can’t get too far away from waste clearance in this post. This time it’s a drug called Rolipram which seems to enhance the brains waste disposal system. It does this by increasing the activity of proteasomes. Neuroscience News describes a proteasome as ‘a hollow, cylindrical structure which chews up defective proteins into smaller pieces that can be recycled into new proteins needed by a cell‘. The scientific paper is published in Nature Medicine titled Tau-driven 26S proteasome impairment and cognitive dysfunction can be prevented early in disease by activating cAMP-PKA signaling. The authors show that Rolipram also reduces the levels of tau, another toxic product involved in Alzheimer’s disease. For an easier read see the Neuroscience News article titled Slowing Alzheimer’s by Speeding Up Brain’s Waste Disposal.
Gene therapy
There is no getting away from it, and gene therapy had to crop up in this post. And yes, it may have a role in the future of Alzheimer’s disease. Researchers genetically treated 10 Alzheimer’s disease patients using nerve growth factor (NGF) gene, and then waited and waited, …and then studied the brains of the subjects. They reported their findings the Journal of the American Medical Association (JAMA) under the title Nerve Growth Factor Gene Therapy Activation of Neuronal Responses in Alzheimer Disease. The details of the study are rather complicated, but it appears the nerve growth factor treatment triggered nerve growth. Doesn’t sound like rocket science but imagine the potential. I only wished they had used a more straightforward title. I prefer the layman’s version in The Guardian simply titled Gene therapy rescues dying cells in the brains of Alzheimer’s patients. Scientific journals really need better headline writers!
Reprogramming astroglia
A cocktail mixture which transforms the brain’s supporting cells into proper nerve cells? Not science fiction it seems. A group of scientists have developed a mixture which could reprogram glial cells into functional brain cells. I came across this in Neurology Times under the title Transforming Glial Cells. For a change, the original research paper is well headlined; it is published in Cell under the title Small Molecules Efficiently Reprogram Human Astroglial Cells into Functional Neurons. The authors show that the cocktail of nine small molecules do the trick by inhibiting glial pathways and activating neuronal pathways. And this all happens within 8-10 days! Too good to be true? Hopefully not.
Looking for more? Here are 13 headlines to further raise the spirits of people with Alzheimer’s disease:
This is a prelude to my upcoming post, How Bright is the Future for Alzheimer’s Disease? In writing that post I came across a few curious reports about Alzheimer’s disease. I thought these reports were not ground-breaking enough to impact on the future of Alzheimer’s disease. They were however all interesting and thought I should share them.
How does your sleep posture increase your risk of Alzheimer’s disease?
Could sleeping on your side help to prevent Alzheimer’s disease? So suggests a study published in Journal of Neuroscience titled The Effect of Body Posture on Brain Glymphatic Transport. What on earth is the glymphatic system!? Wikipedia says it’s a functional waste clearance pathway for the mammalian central nervous system. The authors showed that rats lying on their side cleared brain waste better than if when lying on their backs or fronts. And this waste includes β amyloid, one culprit behind Alzheimer’s disease.If only things were this simple. But just so you know, I now sleep on my side!
Which fatigue-banishing medication may improve Alzheimer’s disease?
Still in slumber-mode, a recent article suggests that the medication, Modafinil, improves cognition. Modafinil is a drug familiar to neurologists who use it to treat conditions typified by excessive sleep, as in narcolepsy. It is also an alerting drug which improves fatigue in conditions such as multiple sclerosis (MS). The article is a systematic review of the evidence on the effect of Modafinil on cognition. It is published in the journal, European Neuropsychopharmacology under the title Modafinil for cognitive neuroenhancement in healthy non-sleep-deprived subjects. Curious, but I don’t see neurologists prescribing this for Alzheimer’s disease anytime soon.
Which fruit juice should you drink to protect yourself from Alzheimer’s disease?
This may seem like a newspaper headline but it is a scientific research published in European Journal of Nutrition titled Consumption of anthocyanin-rich cherry juice for 12 weeks improves memory and cognition in older adults with mild-to-moderate dementia. In the study, 49 people with mild to moderate dementia were given anthocyanin-rich cherry juice over 12 weeks. The authors reported that cherry juice significantly improved verbal fluency, and both long- and short-term memory. Cherry juice is supposedly rich in anthocyanin, a flavonoid, and this is a cognitive enhancer. I wouldn’t run out and stock on cherry juice yet: the number of participants in the study was small, and the duration of the study too small, to make any conclusions. But a curious finding none-the-less.
Which bugs are linked to Alzheimer’s disease?
This is probably the most curious of the questions. The headline from Scientific Reports says Different Brain Regions are Infected with Fungi in Alzheimer’s Disease. The authors of the report show that the brains of people with Alzheimer’s disease, unlike the brains of control subjects, are infiltrated with fungi. If you didn’t have a reason to keep away from fungi before, now you have a curious one.
![By uncredited - Images from the History of Medicine (NLM) [1], Public Domain, https://commons.wikimedia.org/w/index.php?curid=11648572](https://theneurologylounge.files.wordpress.com/2016/07/alois_alzheimer_002.jpg)
![By Carl Vandyk (1851–1931) - [No authors listed] (July 1937). "S. A. Kinnier Wilson". Br J Ophthalmol 21 (7): 396–97. PMC: 1142821., Public Domain, https://commons.wikimedia.org/w/index.php?curid=11384670](https://theneurologylounge.files.wordpress.com/2016/07/samuel_alexander_kinnier_wilson.jpg)
