Posted on 07/15/2016 9:06:35 PM PDT by Alannnnnn
Alzheimer’s disease (AD) is an age-related neurodegenerative disease that is characterized by a progressive loss of memory associated with other cognitive sphere deficits interfering with social and occupational functioning. The global prevalence of AD was estimated at 26.55 million in 2006. During several years preceding the diagnosis of dementia, there is a gradual cognitive decline with a continuum from the predementia stage to the other stages of the disease. Current treatment strategies address impairments of cholinergic and glutamatergic systems. The cholinergic hypothesis was initially presented over 25 years ago and suggests that a dysfunction of acetylcholine containing neurons in the brain contributes substantially to the cognitive decline observed in those with AD. The cholinergic hypothesis of AD states that cholinergic neurons in the basal forebrain are severely affected in the course of the disease, and that the resulting cerebral cholinergic deficit leads to memory loss and other cognitive and non-cognitive symptoms, which are characteristic of the disease. Thus, cholinesterase inhibitors (ChEIs) have long been the cornerstone of treatment for patients with AD. Excessive glutamate levels in the cerebral cortex of AD patients have also been hypothesized to contribute to cognitive deficits in AD. Memantine, a moderate affinity N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, is postulated to counteract this effect. However, the effects of these treatments are limited or controversial and they do not modify disease progression.
Currently available evidence strongly supports the position that AD is mainly characterized neuropathologically by the presence of two kinds of protein aggregates: extracellular plaques of Abeta-peptide and intracellular neurofibrillary tangles (NFTs). The initiating event in AD could be related to abnormal processing of ß-amyloid (Aß) peptide, ultimately leading to formation of Aß plaques in the brain. This process occurs while individuals are still cognitively normal. Abeta is a highly aggregatory neurotoxic peptide, derived from the enzymatic cleavage of a membrane protein, the amyloid precursor protein (APP). The 42-residue form of the peptide (Abeta-42) is more prone to aggregation than the shorter and less hydrophobic 40-residue form (Abeta-40). The pathological long term accumulation of toxic oligomeric Abeta assemblies could have a causal role in the onset and progression of the disease.
APP is processed by beta and gamma-secretases via the amyloidogenic pathway to produce the toxic variety of Abeta (Abeta-42). The nonamyloidogenic pathway results from alpha-secretase cleavage within the Abeta sequence of APP. According to ABeta peptide cascade hypothesis, ABeta triggers all of the pathological features of the disease, from tau hyperphosphorylation to synaptic dysfunction and neuronal cell death. Even though ABeta has an important role in the AD pathogenesis, different findings speak in favour of a less linear pathophysiology. Patients with sporadic cerebral amyloid angiopathy show great levels of amyloid pathology which is not correlated with cognitive symptoms, and old cognitively normal individuals sometimes exhibit cortical Abeta with almost no tangles. This suggests that amyloid alone is insufficient to explain AD phenotype.
Another hypothesis states that Abeta toxicity could be tau dependent or acts in parallel with tau. After a lag period, which varies from patient to patient, neuronal dysfunction and neurodegeneration become the dominant pathological processes. Neurofibrillary tangles are intraneuronal aggregates of paired helical filaments (PHFs) composed of an abnormally hyperphosphorylated intracellular tau protein. Tau normally binds and stabilizes microtubules, the main component of the cellular cytoskeleton. Hyperphosphorylated and aggregated tau lacks its functions and disrupts neuronal transport. It also acts as a toxic stimuli that has an important impact on the viability of neurons: proteolytic cleavage of free tau could generate neurotoxic fragments and abnormal tau sequesters normal tau, MAP1 and MAP2 (other Microtubule-Associated Proteins).
In AD, the interaction between deposition of Abeta and hyperphosphorylation of tau is still controversial. Tau could become hyperphosphorylated in response to a disturbance in the balance of physiological kinase/phosphatase activities, which may be initiated by a neurotoxic onset. Abeta and tau could interfere in an original way contributing to a cascade of events leading to the activation of the apoptotic cell death cascade, neuronal death, and transmitter deficits. In the same way, abnormal tau could potentiate Abeta toxicity as disruption of tau processing remains a necessary event in the neurodegenerative cascade and post mortem analyses show that the degree of tau-related pathology correlates much better with the severity of the dementia than does the Abeta burden.
Recent advances in understanding AD pathogenesis have led to the development of numerous compounds that might modify the disease process. Investigation for novel therapeutic approaches targeting the presumed underlying pathogenic mechanisms is a major focus of research on AD and it is expected that disease-modifying medications will emerge. Cerebrospinal fluid (CSF) concentrations of Abeta-42 and tau protein could provide good accuracy in discriminating patients with Alzheimer’s disease from control subjects, especially for early stages of the disease. These biomarkers give new possibilities for early clinical trials in AD. This article exposes general classes of potential disease-modifying therapies under clinical investigation for the treatment of AD.
Welcome to Free Republic!
bfl
Alzheimer’s is such a sad disease; I hope they find a cure soon.
Thanks for the article, newbie! :)
Like it or not your brain has cannabinoid receptors. Was not this plant designed for us, by The One that designed us? This is why cannabinoids stay in your body for such a long time. It is NOT a foreign substance.
Great post for a newbie!
Welcome to your new home...Free Republic. :-)
I have never tried it [asthma]
But IMO it should be legal.
The constitution does not give the feds the right to control it! States however do have the right to control its use.
Clarence Thomas agrees with me.
FWIW info: an article at PeoplesPharmacy.com/org
describes that the beginnings of AL can be seen in
the eye — looong before other symptoms.
The good news is that there is something that at that
point can be done about it. Nutrition.
Obama and Grayson along with Dr Peter Singer of Princeton already have a successful treatment.
Zyklon B.
They’d better hurry up.
Some what like your eye doc finds diabetes before your doc does?
As I’ve been having vision issues for the past 7 months, been to both Retinologist and Cornea specialist, all give clean bill of eye health. Refraction specialist is next. Long drawn out process, been without glasses for 7 months. So every thing on the computer is blown up and still a blur, driving is very restricted like to the grocery store 2 miles away. Refraction won’t stay stable. Leads back to having cataract surgery one 16 yrs ago the other 6 yrs ago. Dry Eye Disease is a common after effect of Cataract and Lasix surgery. As well as developing Astigmatism you didn’t have before.
Gosh, feeling sorry for you. I have my own problems, but not that bad.
Over the years I have taken matters into my own hands and learned some things.
I have to figure out my own Rx because the eye dr cant. Do a lot of using additional *glasses* overtop of the Rx glasses (plus lenses over my minus Rx).
From what you said, not sure if you need plus lenses or minus ones (as for near-sighted).
But some suggestions in case you havent tried: I get plus lenses as from Walmart/Walgreens etc. more or less $$ as $6 -$12 and on up. You can try their various strengths in the store, to see.
Adlens is a brand, among others, that are available to purchase, no Rx necessary. I get online, but some stores carry — higher priced. Each eye lens can be adjusted separately within a limited range of + to -.
https://adlens.com/ They have had sales, and seem to be developing newer and newer models.
Let me know if you think I might be able to help you any more.
+ & - lenses, focal length is different in each eye. There is a fancy name for it I can’t spell. OD +200 -75 x 135 right eye, left OS +350 -50 x 060 was my April reading. June reading was worse in the left eye.
The glasses available OTC have no Astigmatism correction so are useless. I’ve found none higher than +250. Need +350 for the left eye. Astigmatism was caused by the cataract surgery. Never had it before hand. Never had glasses until I was 32 and needed just plain readers, went on to bifocals then trifocals, when that happened went to the progressive lenses and have been very pleased with them and even with some of the draw backs they have they work great. Time has seen a lot of improvement in them. I buy the best Zeiss.
Magnifying glass x 16 with led lights isn’t to far from hand when I need to read all that tiny font sizes on forms or boxes. Driving is limited to the grocery store. Good thing I’m married and have a built in driver, who has vision issues of his own, thanks to NAVY (20 yr career flight deck) cleaning chems putting holes in his vision Retinitis, and then developing age related glaucoma. He still sees better than I do.
The fact the left eye changes from 20/40-20/60 in a few days is the big factor now. It is not stable enough for a pair of glasses script. That machine can get me close, but does not fine tune, they have to go the old fashion way of mock glasses and keep changing out the lenses until I tell them what is best. Have another refraction scheduled for the 8th of Aug. Since vision in the left eye keeps wandering day to day, I don’t expect a script for glasses any time soon, but do expect a trip to Refraction Specialist and talking Lasix to fix the issue. Medicare/Tricare Life do not consider Lasix a needed surgery even for a medical condition.
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