Symptomatic and Nonamyloid/Tau Based Pharmacologic Treatment for Alzheimer Disease

Aisen, Paul S.; Cummings, Jeffrey L.; Schneider, Lon S.

doi:10.1101/cshperspect.a006395

Cited by 65 publications

(42 citation statements)

References 99 publications

(90 reference statements)

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“…Current treatments are palliative at best and newer therapies remain unproven. Knowing who is a risk and why will make prevention and management easier in the future (Aisen et al 2011; Lee et al 2011; Schenk et al 2011). …”

Section: Discussionmentioning

confidence: 99%

Epidemiology of Alzheimer Disease

Mayeux¹,

Stern²

2012

Cold Spring Harbor Perspectives in Medicine

792

454

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The global prevalence of dementia has been estimated to be as high as 24 million, and is predicted to double every 20 years until at least 2040. As the population worldwide continues to age, the number of individuals at risk will also increase, particularly among the very old. Alzheimer disease is the leading cause of dementia beginning with impaired memory. The neuropathological hallmarks of Alzheimer disease include diffuse and neuritic extracellular amyloid plaques in brain that are frequently surrounded by dystrophic neurites and intra-neuronal neurofibrillary tangles. The etiology of Alzheimer disease remains unclear, but it is likely to be the result of both genetic and environmental factors. In this review we discuss the prevalence and incidence rates, the established environmental risk factors, and the protective factors, and briefly review genetic variants predisposing to disease.

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Section: Discussionmentioning

confidence: 99%

Epidemiology of Alzheimer Disease

Mayeux¹,

Stern²

2012

Cold Spring Harbor Perspectives in Medicine

792

454

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“…The current treatments for AD are acetylcholinesterase inhibitor donepezil (Aricept), rivastigmine tartrate (Exelon), galantamine hydrobromide (Razadyne), and noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptor memantine hydrochloride (Namenda), which were approved by the Food and Drug Administration in 1996, 1998, 2001, and 2003, respectively (reviewed in [2]). Numerous additional medications and substances have also been investigated, aiming to treat or prevent AD.…”

Section: Introductionmentioning

confidence: 99%

Chronic Treatment with Anesthetic Propofol Improves Cognitive Function and Attenuates Caspase Activation in Both Aged and Alzheimer's Disease Transgenic Mice

Shao

Zhang

Dong

et al. 2014

JAD

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There is a need to seek new treatment(s) for Alzheimer's disease (AD). A recent study showed that AD patients may have decreased levels of functional GABA receptors. Propofol, a commonly used anesthetic, is a GABA receptor agonist. We therefore set out to perform a proof of concept study to determine whether chronic treatment with propofol (50 mg/kg/week) can improve cognitive function in both aged wild-type (WT) and AD transgenic (Tg) mice. Propofol was administrated to the WT and AD Tg mice once a week for 8 or 12 weeks, respectively. Morris water maze was used to assess the cognitive function of the mice following the propofol treatment. Activation of caspase-3, caspase-9, and caspase-8 was investigated using western blot analysis at the end of the propofol treatment. In the mechanistic studies, effects of propofol, amyloid-β protein (Aβ), and GABA receptor antagonist flumazenil on caspase-3 activation and opening of the mitochondrial permeability transition pore were assessed in H4 human neuroglioma and mouse neuroblastoma cells by western blot analysis and flow cytometry. Here we showed that the propofol treatment improved cognitive function and attenuated brain caspase-3 and caspase-9 activation in both aged WT and AD Tg mice. Propofol attenuated Aβ-induced caspase-3 activation and opening of the mitochondrial permeability transition pore in the cells, and flumazenil inhibited the propofol's effects. These results suggested that propofol might improve cognitive function via attenuating the Aβ-induced mitochondria dysfunction and caspase activation, which explored the potential that anesthetic propofol could improve cognitive function in elderly and AD patients.

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“…A much hoped-for outcome of the intensive therapeutic research reviewed by Schenk et al (2011), Lee et al (2011), andAisen et al (2011) is that at least one of the agents currently in phase 2 or 3 clinical trials will have shown sufficient efficacy and safety to have been approved as the first disease-modifying treatment for AD. However, even if this central goal is only achieved after 2020, it has become apparent that a new diagnostic and therapeutic paradigm is entering the AD field.…”

Section: Clinical Trials and Treatmentmentioning

confidence: 99%

Alzheimer Disease in 2020

Holtzman

Mandelkow

Selkoe

2012

Cold Spring Harbor Perspectives in Medicine

100

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Remarkable advances in unraveling the biological underpinnings of Alzheimer disease (AD) have occurred during the last 25 years. Despite this, we have made only the smallest of dents in the development of truly disease-modifying treatments. What will change over the next 10 years? While the answer is not clear, we make several predictions on the state of the field in 2020, based on the rich knowledge described in the other contributions in this collection. As such, our predictions represent some of the principal unresolved questions that we believe deserve special investigative attention in the coming decade.

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Symptomatic and Nonamyloid/Tau Based Pharmacologic Treatment for Alzheimer Disease

Cited by 65 publications

References 99 publications

Epidemiology of Alzheimer Disease

Epidemiology of Alzheimer Disease

Chronic Treatment with Anesthetic Propofol Improves Cognitive Function and Attenuates Caspase Activation in Both Aged and Alzheimer's Disease Transgenic Mice

Alzheimer Disease in 2020

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