The Mechanical Cause of Age-Related Dementia (Alzheimer's Disease): The Brain is Destroyed by the Pulse

2015 ◽  
Vol 44 (2) ◽  
pp. 355-373 ◽  
Author(s):  
Jonathan Stone ◽  
Daniel M. Johnstone ◽  
John Mitrofanis ◽  
Michael O'Rourke
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Age Related ◽  
The Brain

scholarly journals Probable Causes of Alzheimer’s Disease

Sci ◽  
2021 ◽  
Vol 3 (1) ◽  
pp. 16
Author(s):  
James David Adams
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Lactic Acid ◽  
Blood Brain Barrier ◽  
Transient Receptor Potential ◽  
Brain Barrier ◽  
Folate Intake ◽  
Blood Brain ◽  
Age Related ◽  
The Brain

A three-part mechanism is proposed for the induction of Alzheimer’s disease: (1) decreased blood lactic acid; (2) increased blood ceramide and adipokines; (3) decreased blood folic acid. The age-related nature of these mechanisms comes from age-associated decreased muscle mass, increased visceral fat and changes in diet. This mechanism also explains why many people do not develop Alzheimer’s disease. Simple changes in lifestyle and diet can prevent Alzheimer’s disease. Alzheimer’s disease is caused by a cascade of events that culminates in damage to the blood–brain barrier and damage to neurons. The blood–brain barrier keeps toxic molecules out of the brain and retains essential molecules in the brain. Lactic acid is a nutrient to the brain and is produced by exercise. Damage to endothelial cells and pericytes by inadequate lactic acid leads to blood–brain barrier damage and brain damage. Inadequate folate intake and oxidative stress induced by activation of transient receptor potential cation channels and endothelial nitric oxide synthase damage the blood–brain barrier. NAD depletion due to inadequate intake of nicotinamide and alterations in the kynurenine pathway damages neurons. Changes in microRNA levels may be the terminal events that cause neuronal death leading to Alzheimer’s disease. A new mechanism of Alzheimer’s disease induction is presented involving lactic acid, ceramide, IL-1β, tumor necrosis factor α, folate, nicotinamide, kynurenine metabolites and microRNA.

scholarly journals Osmotin-loaded magnetic nanoparticles with electromagnetic guidance for the treatment of Alzheimer's disease

Nanoscale ◽  
2017 ◽  
Vol 9 (30) ◽  
pp. 10619-10632 ◽  
Author(s):  
Faiz Ul Amin ◽  
Ali Kafash Hoshiar ◽  
Ton Duc Do ◽  
Yeongil Noh ◽  
Shahid Ali Shah ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Magnetic Nanoparticles ◽  
Neurodegenerative Disease ◽  
Amyloid Beta ◽  
Age Related ◽  
Electromagnetic Guidance ◽  
The Brain

Alzheimer's disease (AD) is the most prevalent age-related neurodegenerative disease, pathologically characterized by the accumulation of aggregated amyloid beta (Aβ) in the brain.

scholarly journals Elevated age-related cortical iron, ferritin and amyloid plaques in APPswe/PS1ΔE9 transgenic mouse model of Alzheimer’s disease

2019 ◽  
pp. S445-S451 ◽  
Author(s):  
H. Svobodová ◽  
D. Kosnáč ◽  
Z. Balázsiová ◽  
H. Tanila ◽  
P.O. Miettinen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Plaques ◽  
Amyloid Plaque ◽  
Free Iron ◽  
Model Of Alzheimer’S Disease ◽  
Age Related ◽  
Concentration Changes ◽  
The Brain ◽  
Important Marker

Iron is very important element for functioning of the brain. Its concentration changes with aging the brain or during disease. The aim of our work was the histological examination of content of ferritin and free iron (unbound) in brain cortex in association with Aβ plaques from their earliest stages of accumulation in amyloid plaque forming APP/PS1 transgenic mice. Light microscopy revealed the onset of plaques formation at 8-monthage. Detectable traces of free iron and no ferritin were found around plaques at this age, while the rate of their accumulation in and around Aβ plaques was elevated at 13 months of age. Ferritin accumulated mainly on the edge of Aβ plaques, while the smaller amount of free iron was observed in the plaque-free tissue, as well as in and around Aβ plaques. We conclude that free iron and ferritin accumulation follows the amyloid plaques formation. Quantification of cortical iron and ferritin content can be an important marker in the diagnosis of Alzheimer’s disease.

scholarly journals Promise and Challenge: The Lens Model as a Biomarker for Early Diagnosis of Alzheimer's Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Tian Tian ◽  
Boai Zhang ◽  
Yanjie Jia ◽  
Zhaoming Li
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Diagnosis ◽  
Accurate Diagnosis ◽  
Lens Model ◽  
Non Invasive ◽  
Diagnosis And Prognosis ◽  
Protein Deposits ◽  
Age Related ◽  
The Brain

Alzheimer’s disease (AD) is the most common form of dementia pathologically characterized by cerebral amyloid-beta (Aβ) deposition. Early and accurate diagnosis of the disease still remains a big challenge. There is evidence that Aβaggregation starts to occur years before symptoms arise. Noninvasive monitoring of Aβplaques is critical for both the early diagnosis and prognosis of AD. Presently, there is a major effort on looking for a reasonably priced technology capable of diagnosing AD by detecting the presence of Aβ. Studies suggest that AD is systemic rather than brain-limited focus diseases and the aggregation of the disease-causing proteins also takes place in lens except the brain. There is a possible relationship between AD and a specific subtype of age-related cataract (supranuclear cataract). If similar abnormal protein deposits are present in the lens, it would facilitate non-invasive diagnosis and monitoring of disease progression. However, there are controversies on the issues related to performance and validation of Aβdeposition in lens as biomarkers for early detection of AD. Here we review the recent findings concerning Aβdeposition in the lenses of AD patients and evaluate if the ocular lens can provide a biomarker for AD.

“Brain-Specific” Nutrients: A Memory Cure?

2002 ◽  
Vol 3 (1) ◽  
pp. 12-38 ◽  
Author(s):  
Mark A. McDaniel ◽  
Steven F. Maier ◽  
Gilles O. Einstein
Keyword(s):  
Alzheimer’S Disease ◽  
Older Adults ◽  
Alzheimer's Disease ◽  
Animal Studies ◽  
Memory Decline ◽  
Memory Tests ◽  
Positive Effects ◽  
Age Related ◽  
Per Se ◽  
The Brain

We review the experimental evaluations of several widely marketed nonprescription compounds claimed to be memory enhancers and treatments for age-related memory decline. We generally limit our review to double-blind placebo-controlled studies. The compounds examined are phos-phatidylserine (PS), phosphatidylcholine (PC), citicoline, piracetam, vinpocetine, acetyl-L-carnitine (ALC), and antiox-idants (particularly vitamin E). In animals, PS has been shown to attenuate many neuronal effects of aging, and to restore normal memory on a variety of tasks. Preliminary findings with humans, though, are limited. For older adults with probable Alzheimer's disease, a single study failed to demonstrate positive effects of PS on memory performance. For older adults with moderate cognitive impairment, PS has produced consistently modest increases in recall of word lists. Positive effects have not been as consistently reported for other memory tests. There is one report of consistent benefits across a number of memory tests for a subset of normal adults who performed more poorly than their peers at baseline. The choline compounds PC and citicoline are thought to promote synthesis and transmission of neurotransmitters important to memory. PC has not proven effective for improving memory in patients with probable Alzheimer's disease. The issue remains open for older adults without serious degenerative neural disease. Research on citicoline is practically nonexistent, but one study reported a robust improvement in story recall for a small sample of normally aging older adults who scored lower than their peers in baseline testing. Animal studies suggest that piracetam may improve neuronal efficiency, facilitate activity in neurotransmitter systems, and combat the age-related decrease in receptors on the neuronal membrane. However, for patients with probable Alzheimer's disease, as well as for adults with age-associated memory impairment, there is no clear-cut support for a mnemonic benefit of piracetam. Vinpocetine increases blood circulation and metabolism in the brain. Animal studies have shown that vinpocetine can reduce the loss of neurons due to decreased blood flow. In three studies of older adults with memory problems associated with poor brain circulation or dementia-related disease, vinpocetine produced significantly more improvement than a placebo in performance on global cognitive tests reflecting attention, concentration, and memory. Effects on episodic memory per se have been tested minimally, if at all. ALC participates in cellular energy production, a process especially important in neurons, and in removal of toxic accumulation of fatty acids. Animal studies show that ALC reverses the age-related decline in the number of neuron membrane receptors. Studies of patients with probable Alzheimer's disease have reported nominal advantages over a range of memory tests for ALC-treated patients relative to placebo groups. Significant differences have been reported rarely, however. Whether ALC would have mnemonic benefits for aging adults without brain disease is untested as far as we know. Antioxidants help neutralize tissue-damaging free radicals, which become more prevalent as organisms age. It is hypothesized that increasing antioxidant levels in the organism might retard or reverse the damaging effects of free radicals on neurons. Thus far, however, studies have found that vitamin E does not significantly slow down memory decline for Alzheimer's patients and does not produce significant memory benefits among early Parkinson's patients. Neither did a combination of vitamins E and C significantly improve college students' performance on several cognitive tasks. In sum, for most of the “brain-specific” nutrients we review, some mildly suggestive effects have been found in preliminary controlled studies using standard psychometric memory assessments or more general tests designed to reveal cognitive impairment. We suggest that future evaluations of the possible memory benefits of these supplements might fruitfully focus on memory processes rather than on memory tests per se.

scholarly journals Changes in Biothiol Levels Are Closely Associated with Alzheimer’s Disease

2021 ◽  
pp. 1-14
Author(s):  
Hui Han ◽  
Feng Wang ◽  
Juanjuan Chen ◽  
Xingxing Li ◽  
Gaoqing Fu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pc12 Cells ◽  
Serum Levels ◽  
Detection Methods ◽  
Serum Homocysteine ◽  
Age Related ◽  
The Status ◽  
The Brain

Background: Serum homocysteine (Hcy) level is considered to be an important biomarker for Alzheimer’s disease (AD); however, the status of Hcy in brain tissue, and the association between brain and serum levels of Hcy in AD patients remain unclear. Objective: We aimed to examine whether the changes of three thiols are consistent in serum of AD patients and the brain of APP/PS1 mice, and to verify the effectiveness of Hcy as a biomarker for early AD detection. Methods: The levels of Hcy, cysteine (Cys), and glutathione (GSH) in Aβ 1–42-treated PC12 cells, the brain and hippocampus of APP/PS1 mouse, and the serum of AD patients were evaluated using ethyl (E)-3-(9-chloro-11-oxo-2,3,6,7-tetrahydro-1H,5H,11H-pyrano[2,3-f] pyrido [3,2,1 -ij] quinolin-10-yl)-2-cyanoacrylate (Probe 1) and ELISA assay or LC-MS. Results: Measurement by Probe 1 revealed a significant increase in Hcy level, and a decrease in Cys and GSH levels in Aβ1–42-treated PC12 cells and the serum of AD patients. The hippocampus and whole brain of APP/PS1 mice also showed a significant increase in Hcy level alongside the accumulation of age-related AD symptoms. The upregulation of Hcy and the downregulation of Cys and GSH were reversed in the Aβ1–42-treated PC12 cells and the brain of APP/PS1 mice when supplemented with VB6. Conclusion: Changes in Hcy, Cys, and GSH levels in the brain of APP/PS1 mice and Aβ 1–42-treated PC12 cells were observed in situ with a new fluorescent probe, which were consistent with the abnormal changes in Hcy, Cys, and GSH levels in the serum of AD patients. VB6 supplementation was successful in ameliorating abnormal increases in Hcy levels.

On the Possible Relevance of Bottom-up Pathways in the Pathogenesis of Alzheimer’s Disease

2020 ◽  
Vol 20 (15) ◽  
pp. 1415-1421 ◽  
Author(s):  
Friedrich Leblhuber ◽  
Kostja Steiner ◽  
Simon Geisler ◽  
Dietmar Fuchs ◽  
Johanna M. Gostner
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Deficits ◽  
Immune Activation ◽  
Significant Proportion ◽  
Microbiome Composition ◽  
Age Related ◽  
Value Changes ◽  
Systemic Infections ◽  
The Brain

Dementia is an increasing health problem in older aged populations worldwide. Age-related changes in the brain can be observed decades before the first symptoms of cognitive decline appear. Cognitive impairment has chronic inflammatory components, which can be enhanced by systemic immune activation. There exist mutual interferences between inflammation and cognitive deficits. Signs of an activated immune system i.e. increases in the serum concentrations of soluble biomarkers such as neopterin or accelerated tryptophan breakdown along the kynurenine axis develop in a significant proportion of patients with dementia and correlate with the course of the disease, and they also have a predictive value. Changes in biomarker concentrations are reported to be associated with systemic infections by pathogens such as cytomegalovirus (CMV) and bacterial content in saliva. More recently, the possible influence of microbiome composition on Alzheimer’s disease (AD) pathogenesis has been observed. These observations suggest that brain pathology is not the sole factor determining the pathogenesis of AD. Interestingly, patients with AD display drastic changes in markers of immune activation in the circulation and in the cerebrospinal fluid. Other data have suggested the involvement of factors extrinsic to the brain in the pathogenesis of AD. However, currently, neither the roles of these factors nor their importance has been clearly defined.

scholarly journals The Sleeping Brain: Harnessing the Power of the Glymphatic System through Lifestyle Choices

2020 ◽  
Vol 10 (11) ◽  
pp. 868
Author(s):  
Oliver Cameron Reddy ◽  
Ysbrand D. van der Werf
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Risk ◽  
Intermittent Fasting ◽  
Waste Products ◽  
Glymphatic System ◽  
Age Related ◽  
Lifestyle Choices ◽  
Brain Ageing ◽  
The Brain

The glymphatic system is a “pseudo-lymphatic” perivascular network distributed throughout the brain, responsible for replenishing as well as cleansing the brain. Glymphatic clearance is the macroscopic process of convective fluid transport in which harmful interstitial metabolic waste products are removed from the brain intima. This paper addresses the glymphatic system, its dysfunction and the major consequences of impaired clearance in order to link neurodegeneration and glymphatic activity with lifestyle choices. Glymphatic clearance can be manipulated by sleep deprivation, cisterna magna puncture, acetazolamide or genetic deletion of AQP4 channels, but how lifestyle choices affect this brain-wide clearance system remains to be resolved. This paper will synthesize existing literature on glymphatic clearance, sleep, Alzheimer’s disease and lifestyle choices, in order to harness the power of this mass transport system, promote healthy brain ageing and possibly prevent neurodegenerative processes. This paper concludes that 1. glymphatic clearance plays a major role in Alzheimer’s pathology; 2. the vast majority of waste clearance occurs during sleep; 3. dementias are associated with sleep disruption, alongside an age-related decline in AQP4 polarization; and 4. lifestyle choices such as sleep position, alcohol intake, exercise, omega-3 consumption, intermittent fasting and chronic stress all modulate glymphatic clearance. Lifestyle choices could therefore alter Alzheimer’s disease risk through improved glymphatic clearance, and could be used as a preventative lifestyle intervention for both healthy brain ageing and Alzheimer’s disease.

scholarly journals Effects of Reactive Oxygen and Nitrogen Species on TrkA Expression and Signalling: Implications for proNGF in Aging and Alzheimer’s Disease

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1983
Author(s):  
Erika Kropf ◽  
Margaret Fahnestock
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Basal Forebrain ◽  
Memory Loss ◽  
Reactive Oxygen ◽  
Neurotrophin Receptor ◽  
Nitrogen Species ◽  
Age Related ◽  
The Brain

Nerve growth factor (NGF) and its precursor form, proNGF, are critical for neuronal survival and cognitive function. In the brain, proNGF is the only detectable form of NGF. Dysregulation of proNGF in the brain is implicated in age-related memory loss and Alzheimer’s disease (AD). AD is characterized by early and progressive degeneration of the basal forebrain, an area critical for learning, memory, and attention. Learning and memory deficits in AD are associated with loss of proNGF survival signalling and impaired retrograde transport of proNGF to the basal forebrain. ProNGF transport and signalling may be impaired by the increased reactive oxygen and nitrogen species (ROS/RNS) observed in the aged and AD brain. The current literature suggests that ROS/RNS nitrate proNGF and reduce the expression of the proNGF receptor tropomyosin-related kinase A (TrkA), disrupting its downstream survival signalling. ROS/RNS-induced reductions in TrkA expression reduce cell viability, as proNGF loses its neurotrophic function in the absence of TrkA and instead generates apoptotic signalling via the pan-neurotrophin receptor p75NTR. ROS/RNS also interfere with kinesin and dynein motor functions, causing transport deficits. ROS/RNS-induced deficits in microtubule motor function and TrkA expression and signalling may contribute to the vulnerability of the basal forebrain in AD. Antioxidant treatments may be beneficial in restoring proNGF signalling and axonal transport and reducing basal forebrain neurodegeneration and related deficits in cognitive function.

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