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What Current Research Is Being Done For Alzheimer’s Disease

What Research Is Being Done

Alzheimer’s Disease

The National Institute of Neurological Disorders and Stroke conducts research related to MID in its laboratories at the National Institutes of Health , and also supports additional research through grants to major medical institutions across the country. Much of this research focuses on finding better ways to prevent, treat, and ultimately cure the vascular dementias, such as MID.

Information from the National Library of Medicines MedlinePlus

The National Institute of Neurological Disorders and Stroke conducts research related to MID in its laboratories at the National Institutes of Health , and also supports additional research through grants to major medical institutions across the country. Much of this research focuses on finding better ways to prevent, treat, and ultimately cure the vascular dementias, such as MID.

Information from the National Library of Medicines MedlinePlus

The National Institute of Neurological Disorders and Stroke conducts research related to MID in its laboratories at the National Institutes of Health , and also supports additional research through grants to major medical institutions across the country. Much of this research focuses on finding better ways to prevent, treat, and ultimately cure the vascular dementias, such as MID.

Information from the National Library of Medicines MedlinePlus

The Devastation Of Alzheimers Disease

With all this said, we are extremely aware of the gradual and cumulative devastation that Alzheimers disease causes, as patients lose their memory and cognitive functioning over time. In late-stage disease, people can no longer hold a conversation or respond to their environment. On average, a person with Alzheimers disease lives four to eight years after diagnosis, but some patients can live up to 20 years with the disease.

The need for treatments is urgent: right now, more than 6 million Americans are living with Alzheimers disease and this number is expected to grow as the population ages. Alzheimer’s is the sixth leading cause of death in the United States.

Although the Aduhelm data are complicated with respect to its clinical benefits, FDA has determined that there is substantial evidence that Aduhelm reduces amyloid beta plaques in the brain and that the reduction in these plaques is reasonably likely to predict important benefits to patients. As a result of FDAs approval of Aduhelm, patients with Alzheimers disease have an important and critical new treatment to help combat this disease.

What Is A Professional Judgment Budget

Each year NIH submits a professional judgment budget that estimates the additional funding needed to advance NIH-supported research into the treatment and prevention of Alzheimers disease and related dementias. The report also summarizes progress and promising research opportunities. Only two other areas of biomedical research cancer and HIV/AIDS follow a similar process designed to accelerate research discovery. This approach is often referred to as a bypass budget because of its direct transmission to the President and then to Congress without modification through the traditional federal budget process.

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Alzheimers And Picks Disease: How They Differ

Clinically, Picks disease differs from AD in affecting personality before memory shows deterioration. Changes in personality can include poor social judgment, disinhibition, vulgarity, and restlessness. Some patients steal or show repetitive, compulsive behaviors. Many patients become irritable, agitated, or depressed. Others are more apathetic.

Self-awareness can be very limited. Language is affected early and eating behaviors are sometimes affected. Incontinence typically occurs earlier than in AD. A peculiar occurrence in some individuals is the development of artistic talents during the progression of dementia. Diagnosis is made on a clinical basis, although genetic testing can confirm some specific subtypes. Atrophy of the frontal and temporal lobes may be apparent on MRI.

Changing The Concept: Ad As A Metabolic Disorder


Clinical studies suggest that diabetes is a major risk factor that contributes to AD pathology. Results from published research indicate that there is a close link between insulin-deficient diabetes and cerebral amyloidosis . Peripheral and central insulin signaling impairments are likely present in both diseases. As a result, type 3 diabetes hypothesis of AD was developed, which attempts to bridge the observed metabolic phenotypes present in diabetes and AD into a coherent framework. Insulin hormone is at a centerpiece of this hypothesis .

Pioglitazone treatment improved memory and cognition in patients with mild-to-moderate AD in a small clinical trial . A larger phase II trial demonstrated improvements in memory retention and attention with rosiglitazone treatment in patients who did not possess an ApoE4 allele . However, phase III trial using rosiglitazone failed to show efficacy in AD . It is important to note that in these trials rosiglitazone was administered alone at dosages that were much lower than those needed to exert a beneficial effect on AD pathophysiology in rodent models of the disease. }NCT00348140 is a recently completed clinical trial in which rosiglitazone was administrated in combination with AChEIs in patients with mild-to-moderate AD. No results have yet been reported.

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Inhibitors Of Tau Aggregation

Hyperphosphorylated Tau aggregates contribute to neurotoxicity observed in AD brain. Methylene blue dye derivatives have shown some promise in inhibiting the formation of Tau aggregates. Methylene blue disrupts the aggregation of Tau, has the ability to inhibit amyloid aggregation, improves the efficiency of mitochondrial electron transport chain, reduces oxidative stress, prevents mitochondrial damage, and is also a modulator of autophagy . The first-generation molecule derived from methylene blue appeared to stabilize AD progression in a clinical trial which lasted 50 weeks. These results motivated researchers to develop a next-generation version of methylene blue, TRx 0237. This compound is a purified derivative of methylene blue which not only inhibits Tau protein aggregation but also dissolves brain aggregates of Tau . Several clinical trials are currently underway to evaluate the potential efficacy of this drug in AD.

What Current Research Is Being Done For Dementia With Lewy Bodies

What research are we funding into dementia with Lewy bodies? Find out in our blog series looking at rarer forms of dementia.

Previously in this series we shined a research spotlight on vascular dementia and frontotemporal dementia.

Now, we’ll be taking a closer look at current research related to dementia with Lewy bodies. But first we need to understand a little more about the disease itself.

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The Amyloid Cascade Hypothesis

A peptide is derived from proteolysis of APP, an integral transmembrane protein found in different cell types, including neurons and glial cells . In humans, alternative splicing produces multiple isoforms of the molecule, with APP695 being the most abundant in the brain . APP is processed into smaller peptide fragments, one of which is A, via cleavage by -, -, and -secretase enzyme protein complexes, which include presenilin and nicastrin molecules . Under physiological conditions, APP is catabolized by the -secretase to produce a soluble sAPP fragment, which remains in the extracellular space, and a carboxy-terminal 83-amino acid fragment, which is anchored in the plasma membrane . sAPP is involved in the regulation of neuronal excitability, improves synaptic plasticity, learning, and memory, and increases neuronal resistance to oxidative and metabolic stresses . In a neuropathological situation, APP is first preferentially cleaved by -secretase 1 , which fragments APP into sAPP and a 99-amino acid membrane-bound fraction . Additional processing of the C99 fragment by -secretase results in the generation of either A or A peptides, thought to be responsible for senile plaque formation . Whilst sAPP is beneficial to the organism, A peptides may cause synaptic loss, decrease neuronal plasticity, alter energy metabolism, induce oxidative stress and mitochondrial dysfunction, and may provoke disruptions in cellular calcium homeostasis .

Compounds Which Promote The Removal Of Amyloid Deposits And Aggregates

What is Alzheimer’s disease?

Another potential treatment option which is centered on the amyloidogenic pathway is to promote the clearance of existing amyloid aggregates and deposits. To achieve this, three different strategies have been evaluated.

2.4.1. Activation of Enzymes That Degrade Amyloid Plaques

Aggregates and amyloid plaques are degraded by multiple proteases including neprilysin, IDE, plasmin, endothelin converting enzyme, angiotensin converting enzyme, and metalloproteinases. Protein levels of these enzymes decrease in AD, which contributes to the formation and accumulation of A . Despite being an attractive strategy for developing disease-modifying drugs, no compounds with this MOA have ever reached advanced clinical development due to the lack of specificity.

2.4.2. Modulation of -Amyloid Transport between the Brain and the Peripheral Circulation

A transport between the CNS and the peripheral circulation is regulated by apolipoproteins low-density lipoprotein receptor-related protein , which increases A outflow from the brain to the blood receptor for advanced glycation end products , which facilitates the transport of A across the blood-brain barrier .

2.4.3. Antiamyloid Immunotherapy

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Types Of Lewy Body Dementia

Lewy body dementia includes two related conditionsdementia with Lewy bodies and Parkinsons disease dementia. The difference between them lies largely in the timing of cognitive and movement symptoms. In dementia with Lewy bodies, cognitive symptoms are noted within a year of parkinsonism, any condition that involves the types of movement changes, such as tremor or muscle stiffness, seen in Parkinsons disease. In Parkinsons disease dementia, movement symptoms are pronounced in the early stages, with cognitive symptoms developing years later.

Dementia with Lewy Bodies

People with dementia with Lewy bodies have a decline in thinking ability that may look somewhat like Alzheimers disease. But over time they also develop movement and other distinctive symptoms that suggest dementia with Lewy bodies. Symptoms that distinguish this form of dementia from others may include:

  • visual hallucinations early in the course of dementia
  • fluctuations in cognitive ability, attention, and alertness
  • slowness of movement, difficulty walking, or rigidity
  • sensitivity to medications used to treat hallucinations
  • REM sleep behavior disorder, in which people physically act out their dreams by yelling, flailing, punching bed partners, and falling out of bed
  • more trouble with complex mental activities, such as multitasking, problem solving, and analytical thinking, than with memory

Parkinsons Disease Dementia

Identifying Who’s At Risk Of Dementia

Experts know that damage to the brain caused by Alzheimer’s disease can start many years before symptoms appear. If people at risk of Alzheimer’s could be identified at an early stage, it is hoped that treatments could be offered that would slow down or even stop the disease.

A major study, called PREVENT, concentrates on people in their 40s and 50s to identify those who are at greater risk of developing Alzheimer’s . It aims to understand what is happening in their brains before symptoms appear.

Specialised brain scans, known as PET scans, have been developed to study two proteins in the brains of those with Alzheimer’s disease. The aim is to increase the understanding of the disease process, and also to identify those people who will benefit most from new drug treatments.

Although PET scans are sometimes used to help with a dementia diagnosis, these highly specialised scans are usually only available as part of clinical trials.

A number of different trials are now under way in people who are currently well but are at increased risk of Alzheimer’s disease.

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Approaches For Improving Multi

Extensive research during the last three decades has provided many insights into the possible molecular mechanisms underlying AD, although a complete understanding of the disease mechanisms is still far from being achieved. Nevertheless, brain imaging, biomarkers, and bioinformatics have provided useful information that can certainly help improve the efficacies of the multi-target strategy for treating AD.

The multifactorial nature of AD dictates the heterogenicity of the molecular mechanisms, pathologies, and clinical symptoms of AD patients. It is therefore possible to stratify AD cases into various subgroups that represent different etiologies, mechanisms, and clinical signs. By analyzing the CSF biomarkers, including the levels of A, tau, and ubiquitin, we were able to stratify AD cases into five subgroups , each of which presents a different clinical profile, suggesting that the disease mechanisms among these groups might not be the same. Indeed, a recent tau immunotherapy clinical trial found effective mostly in those patients who had increased CSF tau levels . Intranasal insulin also showed different efficacies in ApoE4 carriers as compared to non-carriers . Very significant advances have been made during the last decade in the studies of AD brain imaging, CSF and plasma biomarkers, and genetic risk factors. These achievements can and should be used for stratifying patients for future AD clinical trials.

Antiamyloidogenic Pathway And Amyloidogenic Route As Strategies For Development Of Therapeutic Treatments Modifying The Course Of Alzheimer’s Disease

Alzheimer Society of Manitoba

In the last two decades, the pharmaceutical industry has focused primarily on the amyloidocentric approach, devoting substantial resources to develop effective AD drugs. However, multiple failures of drug candidates in clinical trials have led researchers to question the feasibility of this strategy . One possible reason for failure is a lack of biomarkers which could reliably identify AD in relatively early stages. It is entirely possible that the patients currently recruited for phase III trials are in such advanced stages of AD that any attempted intervention is probably useless. Therefore, new diagnostic tools capable of early detection are sorely needed. In the meantime, there is still a number of novel treatments under development, which target the amyloidogenic route. In order to reduce A generation from the APP, – and -secretase inhibition and the potentiation of -secretase activity have been considered.

Selective -secretase modulators may, in theory, be developed in such a way as to avoid the adverse events associated with general enzyme inhibition. The goal of such treatments is to block APP processing without interfering with other signaling pathways like Notch .

The idea that the long-term use of NSAIDs could confer some protection against AD generated some interest in NSAIDs as a treatment potentially useful for reducing A levels. However, negative results reported in clinical trials with NSAIDs suggest that this hypothesis requires further refinement .

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Setting The Federal Research Agenda

NIH takes a collaborative, methodical approach to reviewing progress, identifying gaps, and setting the future agenda for research into Alzheimers disease and related dementias. NIH funding in this area is guided by gaps and opportunities identified in researchsummits, which alternate yearly to focus on Alzheimers disease, Alzheimers disease-related dementias, or dementia care and services.Smaller, focused workshops are held more frequently on specific aspects of this research.

NIH outlines its Alzheimers research efforts in theNIH AD/ADRD Research Implementation Milestones, a research framework detailing specific steps and success criteria toward achieving the goals of theNational Plan to Address Alzheimer’s Disease. The milestones also showcase funding initiatives, accomplishments, and highlights of progress toward accomplishing the National Plan goals.

NIHs research progress is highlighted in the annualAlzheimers and related dementias professionaljudgment budget, which is submitted to Congress each year.

Research: The Road Ahead

There is a great deal to learn about LBD. At a basic level, why does alphasynuclein accumulate into Lewy bodies, and how do Lewy bodies cause the symptoms of LBD? It is also of increasing interest to the Alzheimers and Parkinsons disease research communities. LBD represents an important link between these other brain disorders, and research into one disease often contributes to better understanding of the others.

Many avenues of research focus on improving our understanding of LBD. Some researchers are working to identify the specific differences in the brain between dementia with Lewy bodies and Parkinsons disease dementia. Others are looking at the diseases underlying biology, genetics, and environmental risk factors. Still other scientists are trying to identify biomarkers , improve screening tests to aid diagnosis, and research new treatments.

Scientists hope that new knowledge about LBD will one day lead to more effective treatments and even ways to cure and prevent the disorder. Until then, researchers need volunteers with and without LBD for clinical studies.

To find out more about clinical trials, talk with a doctor or visit the National Institutes of Health Web site at

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Caring For A Person With Lewy Body Dementia

As someone who is caring for a person with LBD, you will take on many different responsibilities over time. You do not have to face these responsibilities alone. Many sources of help are available, from adult day centers and respite care to online and in-person support groups.

Below are some important actions you can take to adjust to your new roles, be realistic about your situation, and care for yourself. See the Resources section for more information.

Educate Others About LBD

Most people, including many healthcare professionals, are not familiar with LBD. In particular, emergency room physicians and other hospital workers may not know that people with LBD are extremely sensitive to antipsychotic medications. Caregivers can educate healthcare professionals and others by:

  • Informing hospital staff of the LBD diagnosis and medication sensitivities, and requesting that the persons neurologist be consultedbefore giving any drugs to control behavior problems.
  • Sharing educational pamphlets and other materials with doctors, nurses, and other healthcare professionals who care for the person with LBD.
  • Teaching family and friends about LBD so they can better understand your situation.

Adjust Expectations

Care for Yourself

Address Family Concerns

Helping Children and Teens Cope with LBD

The organizations listed in the Resources section can help with information about caregiver services and support.

Inhibitors Of Tau Hyperphosphorylation

New research looking to identify Alzheimers disease through blood test

CDK5 belongs to the family of serine/threonine cyclin-dependent kinases and is responsible for a number of physiological functions within the CNS, including neurite outgrowth and the regulation of axonal development . CDK5 catalytic activity is dependent on its direct association with p35, key regulator of CDK5 signaling. This cofactor is cleaved by a nonlysosomal protease calpain in a calcium-dependent manner . Conversion of p35 to p25 results in prolonged activation and mislocalization of CDK5. Due to the increases in intracellular calcium levels observed in the brains of AD patients, pathological activation of CDK5 occurs, resulting in hyperphosphorylation of Tau and neuronal cell death . CDK5 inhibition may thus also be potentially considered as a possible drug target. Currently existing CDK5 inhibitors roscovitine and flavopiridol have demonstrated neuroprotective properties in in vitro and in vivo models of excitotoxicity, ischemia, and neurodegeneration .

Phosphatase activation has also been considered as a possible drug target. Currently, there is only one protein phosphatase 2 agonist in development. Sodium selenite is undergoing phase II trials in Australia . Experimental studies have shown that sodium selenate reduces Tau phosphorylation, both in cell culture and in mouse models of the disease . VEL015 administration to rodents have resulted in significant cognitive improvements and substantial reduction of neurodegenerative phenotype.

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