Articles

Autophagic/lysosomal dysfunction in Alzheimer’s disease

Autophagy serves as the sole catabolic mechanism for degrading organelles and protein aggregates. Increasing evidence implicates autophagic dysfunction in Alzheimer’s disease (AD) and other neurodegenerative d...

Authors: Miranda E Orr and Salvatore Oddo

Predictors of decline in walking ability in community-dwelling Alzheimer’s disease patients: Results from the 4-years prospective REAL.FR study

The aim of this study was to explore the predictors of decline in walking ability in patients with Alzheimer’s disease (AD).

Authors: Yves Rolland, Christelle Cantet, Philipede Souto Barreto, Matteo Cesari, Gabor Abellan van Kan and Bruno Vellas

Neuroprotective effects of donepezil against cholinergic depletion

Intraparenchymal injections of the immunotoxin 192-IgG-saporin into medial septum and nucleus basalis magnocellularis causes a selective depletion of basal forebrain cholinergic neurons. Thus, it represents a ...

Authors: Debora Cutuli, Paola De Bartolo, Paola Caporali, Anna Maria Tartaglione, Diego Oddi, Francesca Romana D’Amato, Annalisa Nobili, Marcello D’Amelio and Laura Petrosini

Propagation of tau pathology in Alzheimer’s disease: identification of novel therapeutic targets

Accumulation and aggregation of the microtubule-associated protein tau are a pathological hallmark of neurodegenerative disorders such as Alzheimer’s disease (AD). In AD, tau becomes abnormally phosphorylated ...

Authors: Amy M Pooler, Manuela Polydoro, Susanne Wegmann, Samantha B Nicholls, Tara L Spires-Jones and Bradley T Hyman

Dominantly Inherited Alzheimer Network: facilitating research and clinical trials

The Dominantly Inherited Alzheimer Network (DIAN) is an international registry of individuals at risk for developing autosomal dominant Alzheimer’s disease (AD). Its primary aims are to investigate the tempora...

Authors: Krista L Moulder, B Joy Snider, Susan L Mills, Virginia D Buckles, Anna M Santacruz, Randall J Bateman and John C Morris

Cerebrospinal fluid biomarkers for Alzheimer disease and subcortical axonal damage in 5,542 clinical samples

The neuronal loss in Alzheimer disease (AD) has been described to affect grey matter in the cerebral cortex. However, in the elderly, AD pathology is likely to occur together with subcortical axonal degenerati...

Authors: Tobias Skillbäck, Henrik Zetterberg, Kaj Blennow and Niklas Mattsson

The role of APP and BACE1 trafficking in APP processing and amyloid-β generation

Neuritic plaques in the brain are a major neuropathological hallmark of Alzheimer’s disease. They are formed by the deposition and aggregation of extracellular amyloid-β protein (Aβ). Aβ is derived from the se...

Authors: Xiaojie Zhang and Weihong Song

Progression of mild Alzheimer’s disease: knowledge and prediction models required for future treatment strategies

Knowledge of longitudinal progression in mild Alzheimer’s disease (AD) is required for the evaluation of disease-modifying therapies. Our aim was to observe the effects of long-term cholinesterase inhibitor (C...

Authors: Carina Wattmo, Åsa K Wallin and Lennart Minthon

Progress in novel cognitive enhancers for cognitive aging and Alzheimer’s disease

Increased knowledge of the biology of synaptic function has led to the development of novel cognitive-enhancing therapeutic strategies with the potential for increased efficacy and safety. This editorial highl...

Authors: Diana W Shineman, Aaron J Carman, Penny A Dacks, Rachel F Lane and Howard M Fillit

Diets involved in PPAR and PI3K/AKT/PTEN pathway may contribute toneuroprotection in a traumatic brain injury

Traumatic encephalopathy has emerged as a significant public health problem. Itis believed that traumatic encephalopathy is caused by exposure to repetitivebrain trauma prior to the initial symptoms of neurode...

Authors: Yasuko Kitagishi and Satoru Matsuda

Potential synergy between tau aggregation inhibitors and tau chaperonemodulators

Tau is a soluble, microtubule-associated protein known to aberrantly formamyloid-positive aggregates. This pathology is characteristic for more than 15neuropathies, the most common of which is Alzheimer’s dise...

Authors: Laura J Blair, Bo Zhang and Chad A Dickey

Would you want to know? Public attitudes on early diagnostic testing for Alzheimer's disease

Research is underway to develop an early medical test for Alzheimer's disease (AD).

Authors: Elizabeth M Wikler, Robert J Blendon and John M Benson

Importance of national plans for Alzheimer’s disease and dementia

Policy makers have a growing interest in Alzheimer’s disease and other dementias, which is seen as the main health and social care challenge of the 21st century. The best way to manage dementia at a country le...

Authors: Marc Wortmann

Apolipoprotein E as a β-amyloid-independent factor in Alzheimer’s disease

APOE, which encodes apolipoprotein E, is the most prevalent and best established genetic risk factor for late-onset Alzheimer’s disease. Current understanding of Alzheimer’s disease pathophysiology posits an impo...

Authors: Andrew B Wolf, Jon Valla, Guojun Bu, Jungsu Kim, Mary Jo LaDu, Eric M Reiman and Richard J Caselli

On the subject of rigor in the study of amyloid β-protein assembly

According to Thomas Kuhn, the success of ‘normal science,’ the science we all practice on a daily basis, depends on the adherence to, and practice of, a paradigm accepted by the scientific community. When grea...

Authors: David B Teplow

Amyloid imaging in clinical trials

The possibility to map amyloid-beta, the Alzheimer’s disease hallmark protein, in vivo opens the application for amyloid imaging in clinical trials with disease-modifying agents. Monitoring change in amyloid b...

Authors: Rik Ossenkoppele, Niels D Prins and Bart NM van Berckel

Regulation of distinct pools of amyloid β-protein by multiple cellular proteases

Alzheimer’s disease (AD) is a progressive, age-related neurodegenerative disorder characterized by extracellular and intracellular deposition of the amyloid β-protein (Aβ). The study of rare, familial forms of...

Authors: Malcolm A Leissring and Anthony J Turner

Cognitive training and cognitive rehabilitation for persons with mild to moderate dementia of the Alzheimer's or vascular type: a review

Cognitive impairments, and particularly memory deficits, are a defining feature of the early stages of Alzheimer's disease and vascular dementia. Interventions that target these cognitive deficits and the asso...

Authors: Alex Bahar-Fuchs, Linda Clare and Bob Woods

Early-onset dementias: diagnostic and etiological considerations

This paper summarizes the body of literature about early-onset dementia (EOD) that led to recommendations from the Fourth Canadian Consensus Conference on the Diagnosis and Treatment of Dementia. A broader dif...

Authors: Mario Masellis, Kayla Sherborn, Pedro Rosa Neto, Dessa A Sadovnick, Ging-Yuek R Hsiung, Sandra E Black, Sadhana Prasad, Meghan Williams and Serge Gauthier

Epidemiology of neurodegeneration in American-style professional football players

The purpose of this article is to review the history of head injuries in relation to American-style football play, summarize recent research that has linked football head injuries to neurodegeneration, and pro...

Authors: Everett J Lehman

Evidence for impaired amyloid β clearance in Alzheimer's disease

Alzheimer's disease (AD) is a common neurodegenerative disease characterized by the accumulation of extracellular plaques and intracellular tangles. Recent studies support the hypothesis that the accumulation ...

Authors: Kristin R Wildsmith, Monica Holley, Julie C Savage, Rebecca Skerrett and Gary E Landreth

A survey of TREM2 antibodies reveals neuronal but not microglial staining in formalin-fixed paraffin-embedded postmortem Alzheimer's brain tissues

Authors: Jun-ichi Satoh, Natsuki Kawana, Yuji Yamamoto, Tsuyoshi Ishida, Yuko Saito and Kunimasa Arima

Knowledge translation: an overview and recommendations in relation to the Fourth Canadian Consensus Conference on the Diagnosis and Treatment of Dementia

The growing population of persons with dementia in Canada and the provision of quality care for this population is an issue that no healthcare authority will escape. Physicians often view dementia as a difficu...

Authors: Cheryl Cook and Kenneth Rockwood

Pharmacological recommendations for the symptomatic treatment of dementia: the Canadian Consensus Conference on the Diagnosis and Treatment of Dementia 2012

While there have been no new medications approved for the treatment of Alzheimer's disease (AD) or other dementias in Canada since 2004, the Canadian Consensus Conference on the Diagnosis and Treatment of Deme...

Authors: Nathan Herrmann, Krista L Lanctôt and David B Hogan

Role of emerging neuroimaging modalities in patients with cognitive impairment: a review from the Canadian Consensus Conference on the Diagnosis and Treatment of Dementia 2012

The Fourth Canadian Consensus Conference on the Diagnosis and Treatment of Dementia (CCCDTD4) was held 3 to 4 May 2012 in Montreal, Quebec, Canada. A group of neuroimaging experts were assigned the task of rev...

Authors: Amer M Burhan, Robert Bartha, Christian Bocti, Michael Borrie, Robert Laforce Jr, Pedro Rosa-Neto and Jean-Paul Soucy

Clinical applications of neuroimaging in patients with Alzheimer's disease: a review from the Fourth Canadian Consensus Conference on the Diagnosis and Treatment of Dementia 2012

In May 2012, the Fourth Canadian Consensus Conference on the Diagnosis and Treatment of Dementia brought together in Montreal experts from around Canada to update Canadian recommendations for the diagnosis and...

Authors: Jean-Paul Soucy, Robert Bartha, Christian Bocti, Michael Borrie, Amer M Burhan, Robert Laforce Jr and Pedro Rosa-Neto

Definitions of dementia and predementia states in Alzheimer's disease and vascular cognitive impairment: consensus from the Canadian conference on diagnosis of dementia

There have been several newly proposed sets of diagnostic criteria for Alzheimer's disease/mild cognitive impairment, advanced by the National Institute of Aging/Alzheimer's Association working groups in 2011 ...

Authors: Howard Chertkow, Howard H Feldman, Claudia Jacova and Fadi Massoud

Diagnosis and Treatment of Dementia: the Fourth Canadian Consensus Conference

Authors: Christopher Patterson and Serge Gauthier

Dementia in the oldest old: a multi-factorial and growing public health issue

The population of oldest old, or people aged 85 and older, is growing rapidly. A better understanding of dementia in this population is thus of increasing national and global importance. In this review, we des...

Authors: Raquel C Gardner, Victor Valcour and Kristine Yaffe

Multiplex biomarkers in blood

Advances in the field of blood biomarker discovery will help in identifying Alzheimer's disease in its preclinical stage, allowing treatment to be initiated before irreversible damage occurs. This review discu...

Authors: Veer Bala Gupta, Ramani Sundaram and Ralph N Martins

Modeling the course of Alzheimer's disease to improve clinical trials: symposium report

In a symposium held at the Clinical Trials in Alzheimer's Disease conference in Monte Carlo, Monaco (29 to 31 October 2012) three different, not mutually exclusive approaches to improve and facilitate clinical...

Authors: René Spiegel, Rachelle S Doody, Suzanne Hendrix and Kristin Kahle-Wrobleski

Exploring the potential of the platelet membrane proteome as a source of peripheral biomarkers for Alzheimer's disease

Peripheral biomarkers to diagnose Alzheimer's disease (AD) have not been established. Given parallels between neuron and platelet biology, we hypothesized platelet membrane-associated protein changes may diffe...

Authors: Laura E Donovan, Eric B Dammer, Duc M Duong, John J Hanfelt, Allan I Levey, Nicholas T Seyfried and James J Lah

What boxing tells us about repetitive head trauma and the brain

Boxing and other combat sports may serve as a human model to study the effects of repetitive head trauma on brain structure and function. The initial description of what is now known as chronic traumatic encep...

Authors: Charles Bernick and Sarah Banks

Progress in Alzheimer's disease research circa 2013: Is the glass half empty or half full?

Authors: Douglas Galasko, Todd E Golde and Philip Scheltens

Comprehensive behavioral characterization of an APP/PS-1 double knock-in mouse model of Alzheimer's disease

Despite the extensive mechanistic and pathological characterization of the amyloid precursor protein (APP)/presenilin-1 (PS-1) knock-in mouse model of Alzheimer's disease (AD), very little is known about the A...

Authors: Scott J Webster, Adam D Bachstetter and Linda J Van Eldik

Alzheimer's disease risk alleles in TREM2 illuminate innate immunity in Alzheimer's disease

Genetic studies have provided the best evidence for cause and effect relationships in Alzheimer's disease (AD). Indeed, the identification of deterministic mutations in the APP, PSEN1 and PSEN2 genes and subseque...

Authors: Todd E Golde, Wolfgang J Streit and Paramita Chakrabarty

Separation of cognitive domains to improve prediction of progression from mild cognitive impairment to Alzheimer's disease

Addressing causes of heterogeneity in cognitive outcomes is becoming more critical as Alzheimer's disease (AD) research focuses on earlier disease. One of the causes of this heterogeneity may be that individua...

Authors: Suzanne B Hendrix and Kathleen A Welsh-Bohmer

The neurotrophic compound J147 reverses cognitive impairment in aged Alzheimer's disease mice

Despite years of research, there are no disease-modifying drugs for Alzheimer's disease (AD), a fatal, age-related neurodegenerative disorder. Screening for potential therapeutics in rodent models of AD has ge...

Authors: Marguerite Prior, Richard Dargusch, Jennifer L Ehren, Chandramouli Chiruta and David Schubert

Advances in blood-based protein biomarkers for Alzheimer's disease

Alzheimer's disease (AD) is a neurodegenerative disorder that accounts for the majority of dementia cases. While research over the past decades has made advances into understanding disease pathology, definite ...

Authors: Lorraine Fuhrmann Clark and Thomas Kodadek

Modeling Alzheimer's disease with non-transgenic rat models

Alzheimer's disease (AD), for which there is no cure, is the most common form of dementia in the elderly. Despite tremendous efforts by the scientific community, the AD drug development pipeline remains extrem...

Authors: Laurent Lecanu and Vassilios Papadopoulos

Targeting norepinephrine in mild cognitive impairment and Alzheimer's disease

The Alzheimer's disease (AD) epidemic is a looming crisis, with an urgent need for new therapies to delay or prevent symptom onset and progression. There is growing awareness that clinical trials must target s...

Authors: Termpanit Chalermpalanupap, Becky Kinkead, William T Hu, Markus P Kummer, Thea Hammerschmidt, Michael T Heneka, David Weinshenker and Allan I Levey

5-HT₆ receptors and Alzheimer's disease

During the past 20 years, the 5-HT₆ receptor has received increasing attention and become a promising target for improving cognition. Several studies with structurally different compounds have shown that not only...

Authors: María Javier Ramírez

Neuroprotective effects of D-Ala²GIP on Alzheimer's disease biomarkers in an APP/PS1 mouse model

Type 2 diabetes mellitus has been identified as a risk factor for Alzheimer's disease (AD). An impairment of insulin signaling as well as a desensitization of its receptor has been found in AD brains. Glucose-...

Authors: Emilie Faivre and Christian Hölscher

Efficacy of SPI-1865, a novel gamma-secretase modulator, in multiple rodent models

Modulation of the gamma-secretase enzyme, which reduces the production of the amyloidogenic Aβ₄₂ peptide while sparing the production of other Aβ species, is a promising therapeutic approach for the treatment of ...

Authors: Robyn M Loureiro, Jo Ann Dumin, Timothy D McKee, Wesley F Austin, Nathan O Fuller, Jed L Hubbs, Ruichao Shen, Jeff Jonker, Jeff Ives, Brian S Bronk and Barbara Tate

DNA-dependent protein kinase and DNA repair: relevance to Alzheimer's disease

The pathological hallmark of Alzheimer's disease (AD), the leading cause of senile dementia, involves region-specific neuronal death and an accumulation of neuronal and extracellular lesions termed neurofibril...

Authors: Jyotshna Kanungo

The effect of cyclodextrin-solubilized curcuminoids on amyloid plaques in Alzheimer transgenic mice: brain uptake and metabolism after intravenous and subcutaneous injection

Curcuminoids may improve pathological conditions associated with Alzheimer's disease. However, their therapeutic potential is limited by their exceedingly low bioavailability after oral administration. A metho...

Authors: Wolfgang W Quitschke, Nicole Steinhauff and Jean Rooney

Plasma tau levels in Alzheimer's disease

Authors: Henrik Zetterberg, David Wilson, Ulf Andreasson, Lennart Minthon, Kaj Blennow, Jeffrey Randall and Oskar Hansson

Have we learnt all we need to know from genetic studies - is genetics over in Alzheimer's disease?

Alzheimer's disease (AD) pathophysiology is mostly (>95%) not inherited in a Mendelian fashion. Such sporadic AD (sAD) forms do not exhibit familial aggregation and are characterized by complex genetic inherit...

Authors: Harald Hampel and Simone Lista

Plasma amyloid beta measurements - a desired but elusive Alzheimer's disease biomarker

Cerebrospinal fluid and positron emission tomography biomarkers accurately predict an underlying Alzheimer's disease (AD) pathology; however, they represent either invasive or expensive diagnostic tools. There...

Authors: Jon B Toledo, Leslie M Shaw and John Q Trojanowski

Biomarkers for Alzheimer's disease in plasma, serum and blood - conceptual and practical problems

Substances produced throughout the body are detectable in the blood, which is the most common biological fluid used in clinical testing. Biomarkers for Alzheimer's disease (AD) have long been sought in the blo...

Authors: Douglas Galasko and Todd E Golde