Causes of Alzheimer's Disease: Other

Other

Support for view of Alzheimer's as form of diabetes

Link between size of hippocampus and progression to Alzheimer's

Post-mortem brain studies reveal features of mild cognitive impairment

Neurons can produce apolipoprotein E

New genetic cause of Alzheimer's disease

Protein identified as cause of memory loss

Reduced insulin in the brain triggers Alzheimer's degeneration

Pin1 enzyme key in preventing onset of Alzheimer's disease

Link between APOE and memory neurotransmitter

Two pathways lead to Alzheimer's disease

Key genetic risk for Alzheimer's linked to myelin breakdown

Study links Alzheimer's and Down’s syndrome

New technique finds higher levels of creatine in Alzheimer’s brains

More light on apoE4 and Alzheimer’s

p25 only good in small doses

Concussions increase chance of age-related cognitive impairment

“Default” brain activity implicated in Alzheimer's disease

How Alzheimer's impacts important brain cell function

Research clarifies how Alzheimer's medicines work

Why diet, hormones, exercise might delay Alzheimer’s

Late-life Alzheimer's begins in midlife

A nicotine by-product implicated in Alzheimer’s

September 2007

Support for view of Alzheimer's as form of diabetes

Research in the last few years has raised the possibility that Alzheimer’s memory loss could be due to a third form of diabetes. A new study clarifies the connection between insulin and Alzheimer’s. It seems that the toxic protein ADDL, found in the brains of individuals with Alzheimer’s, removes insulin receptors from nerve cells, rendering those neurons insulin resistant. The findings suggest that some existing drugs now used to treat diabetic patients may be useful for Alzheimer’s treatment.
The findings were published online August 24 in FASEB Journal.   Full reference
http://www.eurekalert.org/pub_releases/2007-09/nu-dst092607.php

May 2006

Link between size of hippocampus and progression to Alzheimer's

A study of 20 older adults with mild cognitive impairment has found that the hippocampus was smaller in those who developed into Alzheimer's during the 3 year period.
The research appeared in the May issue of the Archives of Neurology. Full reference
http://www.eurekalert.org/pub_releases/2006-05/uoc--rml050406.htm

Post-mortem brain studies reveal features of mild cognitive impairment

Autopsies have revealed that the brains of patients with mild cognitive impairment display pathologic features that appear to place them at an intermediate stage between normal aging and Alzheimer's disease. For instance, the patients had begun developing neurofibrillary tangles, but the number of plaques was similar to that in healthy patients. All patients with mild cognitive impairment had abnormalities in their temporal lobes, which likely caused their cognitive difficulties, and many also had abnormalities in other areas that did not relate to the features of Alzheimer's disease. In a second study, of 34 patients with mild cognitive impairment who had progressed to clinical dementia before their deaths, 24 were diagnosed (post-mortem) with Alzheimer’s, and 10 with other types of dementia. As in the other study, all patients had abnormalities in their temporal lobes.
The two studies appeared in the May issue of Archives of Neurology. Full reference 2nd
http://www.eurekalert.org/pub_releases/2006-05/jaaj-pbs050406.htm

Neurons can produce apolipoprotein E

Apolipoprotein E has been known to be synthesized in the brain in support cells such as astrocytes, microglia, and ependymal layer cells. Controversial for the last decade has been the question of whether or not neurons can produce apoE. Using a unique mouse model, researchers have now demonstrated that neurons can produce apoE, but only in response to injury to the brain.
The study was published in the May 10 issue of the Journal of Neuroscience. Full reference
http://www.eurekalert.org/pub_releases/2006-05/gi-gsp051006.htm

April 2006

New genetic cause of Alzheimer's disease

Amyloid protein originates when it is cut by enzymes from a larger precursor protein. In very rare cases, mutations appear in the amyloid precursor protein, causing it to change shape and be cut differently. The amyloid protein that is formed now has different characteristics, causing it to begin to stick together and precipitate as amyloid plaques. A genetic study of Alzheimer's patients younger than 70 has found genetic variations in the promoter that increases the gene expression and thus the formation of the amyloid precursor protein. The higher the expression (up to 150% as in Down syndrome), the younger the patient (starting between 50 and 60 years of age). Thus, the amount of amyloid precursor protein is a genetic risk factor for Alzheimer's disease.
The findings will appear in the June issue of The American Journal of Human Genetics. Full reference
http://www.eurekalert.org/pub_releases/2006-04/vfii-rda041906.htm

March 2006

Protein identified as cause of memory loss

Researchers have identified a substance in the brain that is proven to cause memory loss, giving drug developers a target for creating drugs to treat memory loss in people with dementia. The substance is a form of the amyloid-beta protein that is distinct from plaques and has been given the name Ab*56. Ab*56 impairs memory independently of plaques or neuronal loss, and may contribute to cognitive deficits associated with Alzheimer's disease.
The research was published in the March 16 issue of Nature. Full reference
http://www.eurekalert.org/pub_releases/2006-03/uom-uom_1031306.htm
http://www.jhu.edu/news_info/news/home06/mar06/memory.html

Reduced insulin in the brain triggers Alzheimer's degeneration

By depleting insulin and its related proteins in the brain, researchers have replicated the progression of Alzheimer's disease – including plaque deposits, neurofibrillary tangles, impaired cognitive functioning, cell loss and overall brain deterioration – in an experimental animal model. Brain deterioration was not related to the pancreas, raising the possibility that Alzheimer's is a neuroendocrine disorder, or a Type 3 diabetes.
The study was published in the Journal of Alzheimer's Disease. Full reference
http://www.eurekalert.org/pub_releases/2006-03/l-rii031606.htm

Pin1 enzyme key in preventing onset of Alzheimer's disease

An enzyme called Pin1, previously shown to prevent the formation of the tangles characteristic of Alzheimer's brains, has now been shown to also play a pivotal role in guarding against the development of the plaques that are also characteristic of Alzheimer's. These findings establish a direct link between amyloid plaques and tau tangles, and provide further evidence that Pin1 (prolyl isomerase) is essential to protect individuals from age-related neurodegeneration.
The study appeared in the March 23 issue of Nature. Full reference
http://www.eurekalert.org/pub_releases/2006-03/hms-nrs032006.htm

February 2006

Link between APOE and memory neurotransmitter

A new link in the complex chain of Alzheimer’s development has been found. It’s been found that receptors that bind apolipoprotein E (APOE) and those that bind glutamate are in fact connected, separated only by a small protein. It may be that inefficient or high levels of APOE are clogging these binding sites, preventing glutamate from activating the processes necessary to form memories. It may also be that the APOE4 variant — associated with Alzheimer's — is less efficient at removing lipid debris in the brain than is APOE2 or APOE3.
The study was published in the February 10 issue of the Journal of Biological Chemistry. Full reference
http://www.eurekalert.org/pub_releases/2006-02/gumc-nrr020906.htm

January 2006

Two pathways lead to Alzheimer's disease

Mild cognitive impairment (MCI), a transitional stage between normal cognition and Alzheimer's disease, has been categorized into two sub-types on the basis of differing symptoms. Those with the amnesic subtype (MCI-A) have memory impairments only, while those with the multiple cognitive domain subtype (MCI-MCD) have other types of mild impairments, such as in judgment or language, and mild or no memory loss. Both sub-types progress to Alzheimer's disease at the same rate. A new imaging technique has now revealed that these types do in fact have different pathologies. The hippocampus of patients with MCI-A was not significantly different from that of Alzheimer's patients (who show substantial shrinkage), but the hippocampus of those with MCI-MCD was not significantly different from that of the healthy controls.
The report appeared in the January issue of Archives of Neurology. Full reference
http://www.eurekalert.org/pub_releases/2006-01/uopm-tpf010606.htm

Key genetic risk for Alzheimer's linked to myelin breakdown

Myelin, the fatty insulation coating the brain's internal wiring, builds up in childhood, and breaks down as we age. Myelin is critical for speedy communication between neurons. A new study supports a growing body of evidence that myelin breakdown is a key contributor to the onset of Alzheimer disease later in life. Moreover, it has also revealed that the severity and rate of myelin breakdown in healthy older individuals is associated with ApoE status. Thus both age, the most important risk factor for Alzheimer disease, and ApoE status, the second-most important risk factor, seem to act through the process of myelin breakdown.
The findings are detailed in the January edition of Archives of General Psychiatry. Full reference
http://www.eurekalert.org/pub_releases/2006-01/uoc--isl122805.htm

Study links Alzheimer's and Down’s syndrome

New research suggests the cognitive problems observed in Alzheimer’s are related to defects in the machinery controlling neuronal connections — PAK enzyme signaling pathways. PAK (p21-activated kinase) enzymes form a family that includes two members (PAK1 and PAK3) that play critical roles in learning and memory. Humans with genetic loss of PAK3 have severe mental retardation. The study reveals that both PAK1 and PAK3 are abnormally distributed and reduced in Alzheimer patients, and that beta-amyloid was directly involved in PAK signaling deficits. The finding suggests therapies designed to address the PAK defect could treat cognitive problems in both patient populations.
The paper was published online January 15 in Nature Neuroscience. Full reference
http://www.eurekalert.org/pub_releases/2006-01/uoc--sid012506.htm

December 2005

New technique finds higher levels of creatine in Alzheimer’s brains

Creatine is involved in the maintaining the energy balance in the brain, but creatine, being small and very soluble, is difficult to detect. A new study has now succeeded in detecting creatine in situ, in brain tissue, and has found relatively large deposits in the hippocampus of Alzheimer’s brains. The finding suggests an overlooked aspect of energy disturbance in Alzheimer's disease, but further research is needed to understand it.
The finding was reported in the November issue of the Journal of Biological Chemistry. Full reference
http://www.eurekalert.org/pub_releases/2005-12/uow-iar122105.htm

More light on apoE4 and Alzheimer’s

A mutant form of a protein that transports cholesterol, apolipoprotein E (apoE) has long been recognized as a causative factor for Alzheimer's disease, but exactly how has been unclear. 299 amino acids are associated with apoE4, but new research has now found which of these amino acids are toxic. These toxic fragments all reside in the mitochondria (the “energy powerhouse” of the cell). The finding suggests a new therapeutic approach, involving blocking interaction of apoE4 fragments with the mitochondria.
The findings were published in the December 20 issue of the Proceedings of the National Academy of Science. Full reference
http://www.eurekalert.org/pub_releases/2005-12/gi-gsl121405.htm

p25 only good in small doses

Elevated levels of a key brain regulatory enzyme called Cdk5 and an associated regulatory protein called p25 have been found in the brains of Alzheimer’s patients. A new mouse study has found that switching on p25 in the hippocampus for only two weeks actually enhanced learning and memory compared to normal mice; however mice in which p25 had been switched on for six weeks showed impaired learning and memory. These mice also showed significant brain atrophy and loss of hippocampal neurons. The two-week pulse of p25 did not cause neurodegeneration and had long-lasting effects on enhancing memory. The researchers suggest that p25 might be produced to compensate for the loss of Cdk5 activity during aging, however chronically high levels lead to neuronal cell death. The findings are consistent with several recent studies suggesting that in the development of Alzheimer’s, compensatory mechanisms that initially enhance neuroplasticity eventually become maladaptive when chronically activated.
The report appeared in the December 8 issue of Neuron. Full reference
http://www.eurekalert.org/pub_releases/2005-12/cp-aje120505.htm

November 2005

Alzheimer's disease onset tied to lapses in attention

A new finding may lead to another tool to detect Alzheimer’s early, and also offers support for the idea that breakdowns in attention may be at the heart of many of the memory problems experienced by Alzheimer’s sufferers. The study, involving 94 older adults (average age mid-70s) who were either healthy controls or in the early stages of Alzheimer’s, found those in the early stages of Alzheimer's disease had greater difficulty shifting attention back and forth between competing sources of information in a dichotic listening task. The finding may also explain why early-stage patients start to struggle with everyday tasks that call for processing a lot of information, such as driving. Prior research has found that performance on dichotic listening predicts accident rates in commercial bus drivers.
[note: this study was briefly reported on in September, but only mentioning its use as an early test]
The study was published in the September issue of Neuropsychology. Full reference
Full text is available at: www.apa.org/journals/releases/neu195687.pdf
http://www.eurekalert.org/pub_releases/2005-11/wuis-ado110905.htm

October 2005

Concussions increase chance of age-related cognitive impairment

A study involving retired National Football League players found that they had a 37% higher risk of Alzheimer's than other U.S. males of the same age. Some 60.8% of the retired players reported having sustained at least one concussion during their professional playing career, and 24% reported sustaining three or more concussions. Those with three or more concussions had a five-fold greater chance of having been diagnosed with mild cognitive impairment and a three-fold prevalence of reported significant memory problems compared to those players without a history of concussion. As the study was based on self-reported answers to the health questions, further studies are needed to confirm the findings, but it does seem likely that head injuries earlier in life increase the chance of developing dementia or mild cognitive impairment.
The study appeared in the October issue of Neurosurgery. Full reference
http://www.eurekalert.org/pub_releases/2005-10/uonc-nsa101005.htm

August 2005

“Default” brain activity implicated in Alzheimer's disease

Here’s an unexpected finding: imaging of the brains of 764 adults of various ages has revealed that the regions that are active when people are in “default mode” — not concentrating on anything in particular, just musing to yourself — are the same regions that develop plaques in Alzheimer’s. They also found that, when asked to concentrate on a specific task, individuals with Alzheimer’s showed increased activity in these posterior cortical regions, rather than the decreased activity seen in young, healthy adults. The researchers speculate that dementia may in fact be a consequence of normal cognitive function — a possibility that hasn’t heretofore been considered. The findings raise the hope of developing methods to detect precursors of the disease long before it develops.
The study appears in the August 24 issue of the Journal of Neuroscience. Full reference
http://www.eurekalert.org/pub_releases/2005-08/hhmi-bai082405.htm

April 2005

How Alzheimer's impacts important brain cell function

Researchers have found that synaptic proteins, proteins involved in brain cell communications, decrease in the brains of Alzheimer's patients compared to healthy brains from people in the same age range. The decrease in the frontal cortex was more severe than in other portions of the brain. They also found synaptic protein levels were even lower in the brains of patients in the early stages of Alzheimer's disease, suggesting that the loss of these proteins happens very early in the disease process. The reduction of synaptic proteins may be caused by mitochondrial dysfunction, a well-documented occurrence in Alzheimer's.
The research was reported in the April issue of the Journal of Alzheimer's Disease. Full reference
http://www.eurekalert.org/pub_releases/2005-04/ohs-ord040605.htm

February 2004

Research clarifies how Alzheimer's medicines work

New research clarifies how cholinesterase inhibitors alleviate mild-to-moderate Alzheimer's. When scientists chemically blocked receptors for an important neurotransmitter called acetylcholine, even healthy young people found it significantly harder to learn and remember – especially in the face of interference. Cholinesterase inhibitors slow the breakdown of acetylcholine. The finding also helps explain why Parkinson's disease, dementia due to multiple strokes, multiple sclerosis and schizophrenia, are all also associated with memory problems — all these conditions, like Alzheimer’s, are associated with lower levels of acetylcholine in the brain.
The study appeared in the February issue of Behavioral Neuroscience. Full reference
(Full text of the article is available at http://www.apa.org/journals/bne/press_releases/february_2004/bne1181223.html )
http://www.eurekalert.org/pub_releases/2004-02/apa-rch020904.htm

February 2004

Why diet, hormones, exercise might delay Alzheimer’s

A theory that changes in fat metabolism in the membranes of nerve cells play a role in Alzheimer's has been supported in a recent study. The study found significantly higher levels of ceramide and cholesterol in the middle frontal gyrus of Alzheimer's patients. The researchers suggest that alterations in fats (especially cholesterol and ceramide) may contribute to a "neurodegenerative cascade" that destroys neurons in Alzheimer's, and that the accumulation of ceramide and cholesterol is triggered by the oxidative stress brought on by the presence of the toxic beta amyloid peptide. The study also suggests a reason for why antioxidants such as vitamin E might delay the onset of Alzheimer's: treatment with Vitamin E reduced the levels of ceramide and cholesterol, resulting in a significant decrease in the number of neurons killed by the beta amyloid and oxidative stress.
The study was published in the February 17 issue of Proceedings of the National Academy of Sciences. Full reference
http://www.eurekalert.org/pub_releases/2004-02/aaft-nsm021004.htm

December 2003

Late-life Alzheimer's begins in midlife

A new model of human brain aging identifies midlife breakdown of myelin, a fatty insulation with very high cholesterol content that wraps tightly around axons (part of the neurons) and enables messages to pass along the “wiring” of the brain speedily, as a possible key to the onset of Alzheimer's disease later in life. Imaging studies and examination of brain tissue shows that the brain's wiring develops until middle age and then begins to decline as the breakdown of myelin triggers a destructive domino affect. It is suggested that genetic factors coupled with the brain's own developmental process of increasing cholesterol and iron levels in middle age help degrade the myelin. The complex connections that take the longest to develop and allow humans to think at their highest level are among the first to deteriorate as the brain's myelin breaks down in reverse order of development. The model suggests that the best time to address the inevitability of myelin breakdown is when it begins, in middle age. Possible preventive therapies include cholesterol- and iron-lowering medications, anti-inflammatory medications, diet and exercise programs and possibly hormone replacement therapy designed to prevent menopause rather than simply ease the symptoms. Education and cognitively stimulating activities may also stimulate the production of myelin.
The report was published in the January edition of Neurobiology of Aging. Full reference
http://www.eurekalert.org/pub_releases/2003-12/uoc--mbc122303.htm

October 2002

A nicotine by-product implicated in Alzheimer’s

A previously unrecognized chemical process has been discovered, by which a chemical called nornicotine, naturally present in tobacco and produced as a metabolite of nicotine, permanently and irreversibly modifies proteins in the body. These modified proteins interact with other chemicals in the body to form a variety of compounds known as advanced glycation endproducts. Advanced glycation endproducts have previously been implicated in numerous diseases including diabetes, cancer, atherosclerosis, and Alzheimer’s disease.
The study was reported in the October 28, 2002 online edition of the Proceedings of the National Academy of Sciences.Full reference
http://www.eurekalert.org/pub_releases/2002-10/sri-aka102402.htm

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