Alzheimer's disease is named after Dr. Alois Alzheimer, a German doctor who first described this disease early in the 20th century.

it is the commonest cause of dementia in Western (developed) societies. probably is too for less developed countries but statistics are not as good there.

development of neurofibrillary tangles and neuritic plaques in the brain cause the symptoms of Alzheimer's and a definite diagnosis of AD is only really available on autopsy.

the disease course:
short term memory usually suffers first, followed by language skills, then judgement and emotional control later. progress is usually slow but can sometimes (rarely) be rapid. most patients with AD live for many years after being diagnosed with this disease.


a good writeup on this: Senile dementia/Alzheimer's type

read all about it: http://www.alzheimers.org/unravel.html

Big symptoms (if you're looking at the brain, that is) include brain shrinkage (some of which is normal as part of the aging process). The folds of the brain in a normal brain are much less pronounced than one afflicted with the disease, these folds are known as intraparietal sulci, and they widen dramatically as the disease progresses.

The hippocampus and amygdala are two major structures that help with memory, and these are also areas heavily damaged by the disease.

The parietal regions are often the most affected, leaving the frontal area less atrophied than usual.

The lateral ventricles also are enlarged.

The atrophy of unhealthy brain tissue causes blood to limited, which, of course, can be a bad thing, accelerating the disease and eventual death.

*knock knock*

An eye peers through the door's crack, much lower than it should be.

"Who are you?"

"I'm Trina... Geoffrey's daughter. Your granddaughter?"

Her hand fumbles at the chain and the door opens wide. I step inside.

I move to hug her - gently, so gently, her bones are brittle now; fragile.

"Do come in. Can I get you a drink?" The motions of polite socialability a thin veneer over the huge uncertainty inside her.

"Do have a seat. This one in the sunshine is nice..."

I sit, and the main part of the day begins.

"Who were you again?"

"Your granddaughter. Your son's daughter."

Your only grandchild now. You won't remember otherwise, so I shalln't remind you"

"Oh yes. I remember. You've put on a lot of weight, haven't you? Where is Geoffrey? He's a lovely boy, isn't he?"

"He didn't come with me"

We're estranged. We don't speak anymore. He doesn't answer my mail

"Oh... Is he still alive?

"Yes, he lives in Brighton with Lesley... You remember Lesley, Geoffrey's wife?"

"I... I remember the name... Did I ever meet her?"

"Yes... You go to their house every Sunday. Geoffrey picks you up and brings you home."

"He's such a lovely boy"

A cat with fur like a summer cloud dabs at her swollen knee, and the first clear emotion since I arrived shines in her face. She pats her lap, and her friend leaps lightly up. Her knotted hands move gracefully as she strokes her darling into a comfortable shape on her thighs.

"My puss is the only true friend I have now... Oh goodness, I talk too much about me. Tell me about yourself. How old are you now?"

I tell her I'm thirty, and she gasps amazedly. "And what do you do?"

"I stay at home, wash clothes, cook meals, make the place nice for my children"

"You have children?"

Yes, Alexander is nine and Jennifer is six. They are both at school at the moment"

"And are you married?"

"I was. He met someone younger."

"Oh that's dreadful."

"Oh, it was for the best really"

and he didn't leave me for my best friend, like your husband.

"and do you have children?"

and now it's beginning

"Yes, Jennifer is five, and Alex is nine. They go to school. That's where they are now."

"Oh... I didn't know any of this... Are you married?"

"I was, yes. But he left me for a younger women"

"Aren't men despicable sometimes?"

I nod sagely, and tell her anecdotes which she told me years ago, of her childhood and youth.

She laughs loudly... and falsely... and says "I've never heard such a funny story in all my life... How old am I again?"

I tell her she's ninety and she reels back... "That can't be right... Ninety? Are you sure?"

I tell her I am, and tell her how pretty the fig tree is looking.

"And do you have any children?" Over and over and over.......

She's hungry. I go to the kitchen and look in her fridge. There are four separate Meals on Wheels meals in there. Untouched. A packet of milk, for her cat. And nothing else.

I take the food and make it hot, then bring it to her on a pretty plate, silver cutlery, a serviette...

She eats slowly, politely.

"Why am I eating here all alone? Don't I have a husband? I thought I was married..."

"You used to have a husband, yes. It was a long time ago"

Don't make me tell you about how he moved in next door, taking the best friend of fifty years away from you

"...Is he dead now?"

I sigh with relief. I can tell the truth without hurting her

"Yes, he's dead now."

"I'll have to chase down a new one then, won't I?"

I smile and ask her why she's want to go to all the trouble of looking after a man, and we laugh together...

It's time for me to leave.

"It was lovely to see you again.... I hope you come back soon...

... What did you say your name was?"

Alzheimer's is the predominant form of senile dementia in older adults. Approximately 50% of persons over age 75 suffer from this disease. The disease potentially affects all domains of cognition though different individuals will manifest different symptoms.

The early stages of Alzheimer's are characterized by a loss of memory, reduced attention span, and loss of verbal communication skills. Individuals in early stages of Alzheimer's are often capable of driving, living on their own and even holding simple jobs. In many individuals the early symptoms are mistaken for old age and the disease is not properly diagnosed till later stages.

As the disease progresses, some individuals will begin to misperceive objects, hallucinate and often hear voices. Some patients will believe they are speaking to a relative who has been dead for some time. They often misidentify close relatives and tend to regress back into early adulthood and sometimes childhood. Some individuals who have immigrated as adults from foreign countries will forget the English they have since learned and remember only their childhood language.

The final stages of Alzheimer's are often painful to endure for close family members. Patients will begin to sleep the majority of the day and forget how to do basic activities of daily life like eating or defecating. Often the requirements of caregiving exceed the capacities of immediate family members and the patient is institutionalized in a nursing home.

While many Alzheimer's patients die from other causes such as cancer, heart attack, pneumonia, and other diseases typical of old age, the neurological degeneration caused by Alzheimer's can cause an individual to die from aspiration.

Alzheimer’s Disease:

Alzheimer's disease is one of the most common problems among the aged. It is devestating for the sufferer, but perhaps more so for the family and friends.

Symptoms:

Alzheimer’s disease has initially innocuous symptoms which appear no different to the normal effects of ageing. However, these symptoms progress to a chronic state. In the early stages, there is memory impairment for recent events and spatial disorientation (e.g., the inability to find objects). Impaired concentration occurs too. Patients can become more aggressive and depressed. Later symptoms are much more severe. All aspects of memory fail, and aphasia (loss of language), apraxia (impairment of purposeful movement), and agnosia (inability to recognise objects) develops. Dementia insofar as judgement and abstract thought also develops. There is just a general impairment of all intellectual function and patients become incapacitated and wasting ensues.

Neuropathological Observations:

Patients appear to have shrinkage of gyri and enlargement of ventricles in the brain. The shrinkage in the frontal and temporal lobes is in the range of 20-30% when the disease has really developed. There is a similar loss of white matter. Imaging techniques have shown in living patients degeneration of tissue in the cerebral cortex (in the frontal, parietal, and temporal lobes), and the amygdala and hippocampus. This cell loss correlates with the degree of dementia and is much greater than normal ageing. There are microscopic abnormalities in neuronal tissue as well, such as plaques and neuronal tangles. There is also up to a 70% loss in the chemical CAT from the temporal and parietal lobes, and the hippocampus. CAT is important to normal brain function. PET has shown that early in the disease, sufferers have hypermetabolism in affected cortical areas. This probably leads to cell death, and may be the result of a compensatory increase for the loss of other cells.

Causes:

There may be some genetic factor at work here since some families have high incidences of Alzheimer’s. However, genetics may not be a major cause because the disorder can occur sporadically. An environmental toxin may be at work, but nothing has really been identified. Studies have linked aluminium to the illness, since it accumulates in the cells of affected areas. But it cannot be said if the aluminium is causative, or a result of the illness. There may be a link to head injuries, as boxers can develop a similar dementia to Alzheimer’s. There is also a “nasal infection theory”. Since Alzheimer’s effects the areas with links to the olfactory system, such as the amygdala, hippocampus, and sensory association areas, whereas it leaves other areas (like the primary motor and visual cortices) untouched, it has been suggested that some toxin may enter through the olfactory bulb and cause this degeneration. However, the nature of such a toxin is unknown, and the olfactory system is only effected in the later stages of the illness. Nasal infection theory has been widely rejected. Given that there are several possible causes, it could, of course, be the case that there are several ways the same disorder could be produced.

Treatment:

There is no treatment for Alzheimer's. The degeneration cannot be halted. Methods to improve the memory problems have been made, but at the neglect of the anti-social behaviour sufferers have. Hydergine causes some improvement to cognitive function by altering neurotransmitters, blood flow, and oxygen usage. The outlook is a little bleak, but the best hope is trying to find the root of the degeneration so that preventative and corrective action can be taken.

Bibliography:

"Brain, Biochemestry and Brain Disorders", P. G. Strange, Oxford University Press, 1992

Oxidation, Mitochondrial damage and Cytotoxicity in Alzheimer’s Disease

Introduction to Alzheimer’s

In 1907, Dr Alois Alzheimer first characterised a disease of memory loss and dementia in elderly patients. It is the most common cause of senile dementia, affecting almost 40% of individuals over 85 years of age. The majority of cases are apparently spontaneous, although a small number of gene mutations are associated with increased risk and earlier onset of disease in some families. The disease involves extensive cortical atrophy, visible on brain sections as abnormally wide sulci.

An explanation of the cause of cell death has long been elusive. Numerous studies have been published that show cell death to be entirely by apoptosis, while another set have shown exclusively necrosis. This obviously suggests that either outcome can occur depending on the situation. What is almost totally certain is the involvement of the plaques of crystalline protein found extensively in Alzheimer’s patient brains: amyloid. A complex picture is emerging of how this amyloid plaque is associated with cell death, with the precise mechanisms becoming increasingly clear.

A likely culprit: The Amyloid-beta peptide

The plaques found in the brains of Alzheimer’s disease sufferers are composed of amyloid fibrils, a material made up of an ordered crystalline precipitate of misfolded protein. Amyloid occurs when some form of environmental stress disrupts the folding pattern of a normally soluble protein. The disrupted form, either broken into fragments or seriously contorted, is no longer soluble in solution. It converts into flat beta-sheets and forms ordered stacks which accumulate into long protofilaments. These twist together like strands in a rope to form fibrils, which aggregate into large plaques such as those seen around brain cells in Alzheimer’s disease.

The protein responsible for Alzheimer’s amyloid is APP, or Alzheimer’s Precursor Protein, is a 770 residue protein whose precise function is unclear. APP can be degraded by proteases along two pathways, only one of which generates the 49-43 residue A-Beta peptides. Which pathway is taken appears to be related to cholesterol levels.

These A-Beta peptides, henceforth referred to as A-Beta, are capable of generating reactive oxygen species, or ROS, through a series of redox reactions with metal ions. They have been shown to do this in vitro and in the absence of cellular material of any kind. As ROS can cause serious damage to cells, this ability immediately suggests a mechanism for cytotoxicity.

It appears increasingly likely that the fully formed plaque itself is not the cause of the disease. Plaque is found in the brains of many elderly people who have retained entirely normal brain function, while some patients with severe Alzheimer’s have only minimal levels. This alone cannot discount the idea that A-Beta is responsible, however, when there is extensive biochemical evidence suggesting its involvement in several different mechanisms of cell damage. While the fully formed and relatively stable amyloid fibrils may not be cytotoxic, the smaller precursor elements are probably responsible. While monomeric A-Beta is not considered neurotoxic, small diffusible oligomers have been shown to be neurotoxic in mice.

The importance of oxidation

The simple explanation for the majority of cell death in Alzheimer’s disease is oxidative damage. Autopsies of Alzheimer’s sufferers show extensive oxidative degradation of proteins and DNA present in areas of the brain affected by the disease. This evidence is backed up by studies which found the progression of neurodegeneration was impeded by the addition of high levels of antioxidants. Oxidative damage would also explain one of the first problems observed in cell cultures when A-Beta is added: rapid mitochondrial problems, usually involving the failure of proton pumping. Such mitochondrial failure is a common symptom of oxidative stress on a cell: mitochondrial enzymes are extremely sensitive to oxidative damage. Worse still, disruption to mitochondrial function can lead to the production of more ROS inside the organelle, exacerbating the damage.

Damage to mitochondrial membrane integrity could very easily kill a cell. If the outer membrane is perforated and Cytochrome c escapes into the cytoplasm, the pathway of internal activation of apoptosis via caspase activation will be triggered. Apoptosis could also possibly be triggered if serious oxidative damage to DNA occurs.

There are also more brute-force ways that attack by ROS can prove lethal to a cell. Disruption of membrane stability, structural proteins or normal enzyme activity could prove sufficiently traumatic to a cell to result in necrosis. Whichever pathway to cell death is involved in any particular case, the importance of oxidative damage is well established. One question remains: how could the A-Beta peptide cause these effects?

The production of radicals

As the importance of oxidation and the creation of ROS has been evident for some time, much thought has gone into investigating the way A-Beta could be responsible. The first and most obvious explanation involves the ability of A-Beta to react with copper and produce reactive species.

A-Beta and copper redox reactions

A-Beta’s ability to insert in bilipid layers ensures the presence of reactive oligomers just outside the cell. There, in close association with the membrane, they may undergo a series of redox reactions with trace levels of copper present in the brain, generating ROS. The close proximity to the membrane means that the most likely result of ROS attack will be lipid peroxidation, damage to channels and transporters and ultimately serious disruption of ion balance. Such disruption puts the cell under significant oxidative stress, with all the associated mitochondrial failure which is an early sign of Aâ toxicity.

Despite the elegance of this model, the precise mechanisms involved were not at all well explained. It now appears that despite its logical merits, experimental evidence indicates that an alternative mechanism is being used.

The role of direct perforation and Calcium influx

Recent studies have indicated that the presence of A-Beta in the membrane alone is not directly related to increases of ROS inside the cell. Two interesting factors were observed: firstly, that ROS generation was dependent on rising intracellular calcium. Secondly, and oddly enough, that rises in ROS are not seen at all in neurons, while they are seen in astrocytes. This suggests that some unique characteristic of astrocytes is responsible for the lion’s share of ROS generation.

The apparent relationship between calcium and ROS depends on the ability of A-Beta amyloid to insert into the membrane and perforate it. This provides an elegant explanation for why single monomers A-Beta are not toxic, but tetramers are: the transmembrane domains of the tetramers can combine to form a pore. This would allow an influx of extracellular calcium. Disruption of the normal homeostatic balance of the cell would result, putting it under a great deal of stress and promoting oxidation.

The relationship between this calcium influx and generation of ROS in astrocytes is explained by the discovery that these cells contain an enzyme previously only identified in immune phagocytes. NADPH oxidase is used by these cells to produce large quantities of ROS for use as a weapon against microbes. It is found associated with mitochondria, and is activated by increased intracellular calcium levels.

Alternatives to oxidative damage: An enzyme binding model

One flaw in the membrane perforation theories is that there is evidence that it does not occur at all in neurons. This, added to the fact that neurons lack NADPH oxidase and thus cannot undergo the mechanism of ROS generation outlined above, raises some interesting questions. It is well established that in Alzheimer’s disease there is extensive neuronal death, and also that A-Beta fibril intermediates are neurotoxic. Are neurons dying because of lack of astrocyte support, or because of the toxic debris released by nearby mass necrosis? The neurotoxicity of A-Beta in pure cultures of neurons suggests otherwise. Is A-Beta causing an alternative mechanism of cell death in neurons?

What is A-Beta AD and how could it be involved?

Yeast-2 hybrid studies of whole-brain homogenates have yielded only one protein which binds to A-Beta peptide, which has subsequently been named A-Beta AD: Amyloid Beta binding Alcohol Dehydrogenase. It has been identified as a mitochondrial enzyme, and knockout models have shown it to be vital for survival in Drosophila. Most interesting is its binding characteristics: once bound to the amyloid fragments, the structure of A-Beta AD was shown to be highly abnormal. The enzyme binding site had clearly been completely disrupted.

Could it be that the presence of amyloid fragments causes mitochondrial toxicity by binding with and deforming a critical enzyme?

An apparently gaping flaw in this argument is the fact that A-Beta is inherently hydrophobic, as reflected by its drive to form amyloid fibrils to protect itself from the surrounding aqueous environment. Why would it leave the relative safety of the membrane and enter the cytoplasm? How and why it does so remains unclear, but there is very convincing evidence that it can be found throughout neurons, particularly in the mitochondria. Recent studies by confocal microscopy show plenty of A-Beta can be found in the mitochondria, along with A-Beta AD. This was supported by immunogold electron microscopy images.

Conclusions

The ability of the A-Beta peptide to cause cell loss in the brain is clearly more complex than was understood a few years ago. Specific mechanisms are now becoming known, providing more possible targets for therapy and prevention. Perhaps most importantly, it is now evident that the fully formed plaque is not toxic and attacking it will not be of clinical use. The reactivity of individual A-Beta peptides is another culprit which has been largely exonerated as the result of recent discoveries. It is the pore-forming, enzyme-binding behaviour of oligomers that needs to be the focus of future research.

An excellent review of this area is by Laura Canevari et al, in Neurochemical Research, Volume 29, pages 637-650: 2004. The study on ABAD colocalisation was by Joyce Lustbader et al, in Science, volume 304, pages 448-452, 2004. This has been a Node your Homework production.

What to do when Alzheimer’s strikes

My Mom was diagnosed with Alzheimer’s 6 years ago, at age 55. There are two things I wish I had known at the time, which I believe would have lessened my grief.

These first days of shock and grief are nearly unbearable. You are grieving the loss of your plans and dreams for the future. You can't avoid this grief; you must accept it. What you can do, however, is avoid unnecessary painful thoughts.

  1. Stay away from the internet for those first few days.

    I am definitely one to rush to the internet to find out more about a difficulty. Termites? Here's who to call! Hangnails? Here's what to do! Usually I find that having more information solves or at least helps a situation. This is not so with Alzheimer’s.
    1. Do not look up information about Alzheimer’s.

      You already have a good idea of what Alzheimer’s is and does. If anything, the facts are probably worse than you imagine. Why put yourself through that now? Do you really need to know the details of what will happen 5 years from now? How will that help? There will be plenty of time later on to learn about the disease and research treatment options. But the treatments currently available will be of little comfort to you today; there is no cure.
    2. Do not look up Alzheimer’s support groups.

      The people corresponding here are in a different place than you. They have worked through the initial grief and the early years and are matter-of-factly trying to find support and answers for their day-to-day problems. But their descriptions of the problems will be frightening to someone who is not there yet.

    Why is this? Why should you not inform yourself as soon as possible about what will happen? The first reason is practical:

    1. It won't seem so bad at the time.

      You probably won’t believe me, but one way or another, you will be able to handle the day-to-day problems that arise. Not that it will be fun, but it will not be as terrible as it all seems at the beginning. I remember grieving those first few days that someday my own mother would not know me, and I also remember that when it did happen, it was no big deal. I don't think I was even sad about it; it just didn't matter all that much.

      The second reason is more philosophical:

    2. You can't handle it.

      A great man once said, "Sufficient unto the day is the evil thereof." There is enough to grieve today, the death of your dreams for a long future with your loved one, without grieving over events years ahead. You are not required to suffer every sorrow of the next 10 years today; only bear today's sorrow today.

    Which brings me to the second thing I wished I had known:

  2. You will smile again.

    You will have happy days. The three best days of my life all happened after the diagnosis, which was by far the worst day of my life. One of those days was less than two months after diagnosis. Am I a shallow person, that I seemingly shrugged off this pain so quickly? The opposite, I hope. This disease will change your life, and not entirely for the worse.

One last tip: have someone you love read you a funny book before you go to bed. Bill Bryson's "I'm a Stranger Here Myself" got me to sleep that night. I will be forever grateful to him, and to the person with the courage to read it to me.

Let's talk about dementia, memory loss, the most common kind being Alzheimer's. There are other kinds: multi-infarct dementia, Pick's, a few treatable dementias. I went to the big national family practice conference a few years ago and one talk radically changed how I follow memory loss and think about it. The first thing was the statistics they gave: 4% of 65 year olds have memory loss and then it increases by 2% a year. Do the math. At 85, it would be 2 times 20 plus 4 for a total of 44%. At 95 we are up to 64%. This changed my practice. I started recommending a screening baseline test for memory loss at 65 so that we could track it.

The second part of the lecture explained how a basic memory test correlated with three stages of memory loss. The test is the MMSE:Mini-Mental Status Exam. It consists of 30 questions which test different parts of the brain. I have done it with people so many times that I have it memorized. Short term memory, concentration, naming objects and stuff that we all hope should be simple: the first question is: what is the year, month, day, date and season? In the last three weeks in clinic I have had two people who scored 13/30. I also met a new woman. She has a caregiver who lives with her. This is a good thing, because she scored 4/30. She should not be left alone, use a stove, microwave, light candles and so forth. One of the people scoring 13 was brought to the emergency room because her car alarm was going off and she couldn't remember how to turn it off. She couldn't answer questions and could not tell the police where she lived. The ER physician, the police and I all filed forms to keep her from driving. I told her son she should not live alone any more. I have been doing MMSE tests on her since 2006: she has scored 26, 18, 19 and now 13.

How does the MMSE correlate with the stages of memory loss? The first stage is the loss of short axons in the brain, scores of about 26 down to 20. Short term memory loss and concentration are affected. The second stage is from 19 down to the low teens. This is the medium length axons in the brain and affects remembering people's names, how to get places, how to perform tasks even if one has been doing them for years. The final stage is the longest axons, scores dropping below 10 and this is when people lose executive function. They can't find words. They may no longer recognize family. They may think that a son is their brother. It is as if they travel back through their memories, losing them as they go. At last they lose any memory of a spouse, family, toilet training and eventually do not care about eating any more. The average lifespan from diagnosis is 7 years.

Once I learned about the different axons being destroyed I understood something that had puzzled me: why behavior may change radically as memory loss progresses, depending on what functions are currently being affected. People have trouble learning new information at one stage and at the next they start getting lost, even driving to very familiar places. I started to track scores on my patients so that I could help explain what was happening to their families. Most people are cared for at home for a very long time; behaviour or incontinence or not recognizing any family are the times when they are moved to a nursing home.

The MMSE is not perfect. Scores are affected by educational background. I think that I'll fool my future doctor for quite a while, because one of the questions is count backwards from 100 by 7s: 93, 86, 79, 72, 65. I have that down really solidly in the memory banks, so I'll get by for longer than I should. Still, the score will drop over time if the memory loss is Alzheimer's. The medicines do help slow the drop for a while.

After my lady with the car alarm was picked up, I called our local neurologist. I received no training in medical school or residency in determining someone's competence, so my question was about the MMSE: was there a score below which a person is probably not competent? That is, to make medical decisions. Our neurologist said he had not been trained in competency either, but he thought below 20. I did some reading: 18 and below is a fairly good measure. One study tested an MMSE and then gave people two medical scenarios. If they scored below 19, for the most part they could not make a medical decision.

The blessing of Alzheimer's or perhaps the irony, is that as it progresses, the person who is losing their memory does not usually seem to mind much. They do not like the MMSE, though I try to make it really gentle. Some people are amazing at covering up. One woman answered every question, saying, "Well, that's a very good question. I think that is an important thing to talk about. That is important." Family members are often in denial and automatically start answering questions for the loved one. Alzheimer's is hardest on the loved ones because they lose the person, bit by bit and axon by axon.

One couple recently asked if I would write a letter explaining the wife's memory loss to their children. The husband initially asked and I asked for the wife's permission. She agreed. They both came in to read the letter. I felt very sad as she read it. After she read it she got out of her chair. I asked her about her back, hoping to distract her a bit. She answered and then turned and looked at the chair. "There's nothing there that is going to help me," she said. I think that she was talking about the letter. Then she said, "You know we love you." So even though it felt terribly uncomfortable to give her the letter and watch her read it, it still was right.

I am coming to terms with my mother’s dementia. What began for me as a sad and horrifying acknowledgement has now become an accepted fact of life. I wrote about this back in October. At that time she was still being taken out of bed twice a day for meals and social gatherings.

Since then her physical condition has deteriorated; she is in her hospital bed 24/7. Her attention span these days is too short to follow television; even with all the naps she takes, the days are certainly long for her. Perhaps that is why, with nothing to do but stare at the ceiling, the stories she tells me are becoming more and more elaborate.

Like many Alzheimer’s patients, she believes she is meeting relatives who have been dead for some time. I visit her daily now; recently every visit has included a long, disjointed narration about my deceased cousin, Buddy. Yesterday’s conversation was typical.

Buddy appears several times a week in the nursing home's chapel with a friend. They are volunteers, entertaining the residents with a mixed selection of songs and piano playing. She tells me Buddy has a wonderful voice, as does his friend. And Buddy is so handsome in his bright green suit.

I am comfortable with this conversation. I make bland comments and agree with her as she rambles on. She is happy; I am content that she is happy. Finally, it is time for me to go.

Someone from the Activities Staff has installed a CD player on my mother’s chest of drawers. As the nursing home is a non-profit Christian home, it is usually playing hymns; I shut it off when I enter so we can talk, then turn it on again when I depart.

Now, as I am leaving, I notice a few CD cases lying next to the player. I leaf through them. All hymns except – Perry Como! She idolized Perry Como years ago. I put it in the machine, tell her I have a surprise for her. Someone she knows.

The smooth lyrics of “If I Loved You” fill the room. I say, “Listen, it’s Perry Como.”

She frowns. “No, that’s not Perry Como. That’s the man who sings with Buddy. He was singing in the chapel earlier this morning. That's him, in there again.”

Apoptosis in Alzheimer's

Apoptosis is Greek which means, “falling from” or “falling away” and is defined by Wolf and Green (2002) as “a conserved cellular suicide program that eradicates excess or potentially dangerous cells”. This necessary program for suicide in cells can also contribute to the progression of some diseases and disorders. One particular disease in which this has become a salient point is Alzheimer’s disease, amongst a list of other disorders and diseases (Chamond, Anon, Aguilar and Pasadas, 1999).

Detection of cell cycle proteins has been found in human and rat models of Alzheimer’s in several studies (Guo et al., 1998; Gibson, 2001). It has also been substantiated through detection of DNA replication that an ectopic cell cycle is involved which precedes neuronal death (Yang et al., 2001; Herrup et al., 2004) which can lead to apoptosis. The pattern of the cell death itself occurs in such a fashion that it is consistent with apoptosis due to the fact that the cells do not lie together but individually (Siegel et al., 2006).

For apoptotic cell death, one would expect to find apoptotic proteins increased – which is exactly what has been found. Guo et al. showed that the Par-4 (Prostate Apoptosis Response-4) protein expression is increased in neurons that are considered “vulnerable”. Later, Guo et al. (2001) showed that their earlier findings to be substantiated. They found that Par-4 increases the secretion of the amyloid β peptide 42 via a caspase-dependent pathway. It was found that inhibition of caspase activity by a broad spectrum inhibitor weakened the Par-4 induced peptide production. Also, implicated is p53 (Cellular tumor antigen p53) protein which is involved in regulation of the cell cycle, DNA repair and can initiate apoptosis. Ohyagi et al. (2005) found that Aβ 42 activates the p53 promoter subsequently leading to p53 induced apoptosis. All these activities interact within the brain of Alzheimer’s patients – specifically the hippocampus to produce the cognitive deficits we see as a result and “support a role for apoptosis” (Siegel et al., 2006).

References

Chamond, R., Anon, J., Aguilar, C. and Pasadas, F. (1999). Apoptosis and disease. Alergologia e Immunologia Clinica, 14, 367-374.

Gibson, R. (2001). Does apoptosis have a role in neurodegeneration? British Medical Journal, 322, 1539-1540.

Guo, Q., Fu, W., Xie, J., Luo, H., Sells, S., Geddes, J. et al. (1998). Par-4 is a mediator of neuronal degeneration associated with the pathogenesis of Alzheimer disease. Nature Medicine, 4, 957-962.

Guo, Q., Xie, J., Chang, X. and Du, H. (2001). Prostate apoptosis response-4 enhances secretion of amyloid β peptide 1-42 in human neuroblastoma IMR-32 cells by a caspase-dependent pathway. Journal of Biological Chemistry, 276, 16040-16044.

Herrup, K., Neve, R., Ackerman, S. and Copani, A. (2004). Divide and die: Cell cycle events as triggers of nerve cell death. Journal of Neuroscience, 24, 9232-9239.

Ohyagi, Y., Asahara, H., Chui, D., Tsuruta, Y., Sakae, N., Miyoshi, K. et al. (2005). Intracellular Aβ42 activates p53 promoter: a pathway to neurodegeneration in Alzheimer’s disease. FASEB Journal, 19, 255-257.

Siegel, G., Albers, R., Brady, S. and Price, D. (2006). Basic Neurochemistry: Molecular, Cellular and Medical Aspects. (7th ed.). London: Elsevier Academic Press.

Wolf, B. and Green, D. (2002). Apoptosis: Letting slip the dogs of war. Current Biology, 12, R177-R179.

Yang, Y., Geldmacher, D. and Herrup, K. (2001). DNA replication precedes neuronal cell death in Alzheimer’s disease. Journal of Neuroscience, 21, 2661-2668.

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