Articles

Modeling the heterogeneity in risk of progression to Alzheimer's disease acrosscognitive profiles in mild cognitive impairment

Heterogeneity in risk of conversion to Alzheimer's disease (AD) among individualswith mild cognitive impairment (MCI) is well known. Novel statistical methods thatare based on partially ordered set (poset) mod...

Authors: Curtis Tatsuoka, Huiyun Tseng, Judith Jaeger, Ferenc Varadi, Mark A Smith, Tomoko Yamada, Kathleen A Smyth and Alan J Lerner

Effects of donepezil 23 mg on Severe Impairment Battery domains in patients with moderate to severe Alzheimer's disease: evaluating the impact of baseline severity

The US Food and Drug Administration approved a 23 mg daily dose of donepezil for treatment of moderate to severe Alzheimer's disease (AD) based on outcomes from a large trial comparing the 23 mg/day dose with ...

Authors: Steven Ferris, Jeffrey Cummings, Daniel Christensen, Rachelle Doody, Martin Farlow, Marwan Sabbagh, Liang Liu, Joan Mackell and Randi Fain

The C9ORF72 mutation brings more answers and more questions

The clinical, neuropsychiatric and neuroimaging features of patients who carry the important new C9ORF72 mutation are discussed in this special series of Alzheimer's Research & Therapy. First reported in November...

Authors: Bruce L Miller

Diverse therapeutic targets and biomarkers for Alzheimer's disease and related dementias: report on the Alzheimer's Drug Discovery Foundation 2012 International Conference on Alzheimer's Drug Discovery

The Alzheimer's Drug Discovery Foundation's 13th International Conference on Alzheimer's Drug Discovery was held on 10-11 September 2012 in Jersey City, NJ, USA. This meeting report provides an overview of Alz...

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

Alcohol-related dementia: an update of the evidence

The characteristics of dementia relating to excessive alcohol use have received increased research interest in recent times. In this paper, the neuropathology, nosology, epidemiology, clinical features, and ne...

Authors: Nicole J Ridley, Brian Draper and Adrienne Withall

Memantine in patients with Alzheimer's disease receiving donepezil: new analyses of efficacy and safety for combination therapy

Memantine and cholinesterase inhibitors potentially offer additional benefits in Alzheimer's disease (AD) when used together. This study assessed the efficacy and safety of combination treatment with memantine...

Authors: Alireza Atri, José L Molinuevo, Ole Lemming, Yvonne Wirth, Irena Pulte and David Wilkinson

¹⁸F-florbetaben Aβ imaging in mild cognitive impairment

¹⁸F-florbetaben and positron emission tomography were used to examine the relationships between β-amyloid (Aβ) deposition, cognition, hippocampal volume, and white matter hyperintensities in mild cognitive impai....

Authors: Kevin Ong, Victor L Villemagne, Alex Bahar-Fuchs, Fiona Lamb, Gaël Chételat, Parnesh Raniga, Rachel S Mulligan, Olivier Salvado, Barbara Putz, Katrin Roth, Colin L Masters, Cornelia B Reininger and Christopher C Rowe

Clinical, imaging, and pathological heterogeneity of the Alzheimer's disease syndrome

With increasing knowledge of clinical in vivo biomarkers and the pathological intricacies of Alzheimer's disease (AD), nosology is evolving. Harmonized consensus criteria that emphasize prototypic illness continu...

Authors: Benjamin Lam, Mario Masellis, Morris Freedman, Donald T Stuss and Sandra E Black

Dose and plasma concentration of galantamine in Alzheimer's disease - clinical application

Patients with Alzheimer's disease (AD) are currently treated with cholinesterase inhibitors, such as galantamine, without actual knowledge of its concentration in plasma. Our objective was to analyse potential...

Authors: Carina Wattmo, Erik Jedenius, Kaj Blennow and Åsa K Wallin

Assessment of psychiatric changes in C9ORF72 frontotemporal dementia

Recent neuroimaging evidence highlights cerebellar atrophy as one feature of frontotemporal dementia (FTD) with C9ORF72 mutation. Interestingly, C9ORF72 patients do not present with classic cerebellar symptoms...

Authors: Michael Hornberger

Does a prion-like mechanism play a major role in the apparent spread of α-synuclein pathology?

Parkinson's disease, the most common movement disorder, results in an insidious reduction for patients in quality of life and ability to function. A hallmark of Parkinson's disease is the brain accumulation of...

Authors: Amanda N Sacino and Benoit I Giasson

Plasma lipoprotein-associated phospholipase A₂ activity in Alzheimer's disease, amnestic mild cognitive impairment, and cognitively healthy elderly subjects: a cross-sectional study

Lipoprotein-associated phospholipase A₂ (Lp-PLA₂) is a circulating enzyme with pro-inflammatory and oxidative activities associated with cardiovascular disease and ischemic stroke. While high plasma Lp-PLA₂ activ...

Authors: Julie E Davidson, Andrew Lockhart, Leslie Amos, Heide A Stirnadel-Farrant, Vincent Mooser, Marc Sollberger, Axel Regeniter, Andreas U Monsch and Michael C Irizarry

NF-κB-regulated, proinflammatory miRNAs in Alzheimer's disease

Abundant neurochemical, neuropathological, and genetic evidence suggests that a critical number of proinflammatory and innate immune system-associated factors are involved in the underlying pathological pathwa...

Authors: Walter J Lukiw

Treatment implications of C9ORF72

Frontotemporal dementia (FTD) is a common dementia syndrome in patients under the age of 65 years with many features overlapping with amyotrophic lateral sclerosis (ALS). The link between FTD and ALS has been ...

Authors: Sharon J Sha and Adam Boxer

Simulations of symptomatic treatments for Alzheimer's disease: computational analysis of pathology and mechanisms of drug action

A substantial number of therapeutic drugs for Alzheimer's disease (AD) have failed in late-stage trials, highlighting the translational disconnect with pathology-based animal models.

Authors: Patrick D Roberts, Athan Spiros and Hugo Geerts

Neuroimaging features of C9ORF72 expansion

Hexanucleotide expansion intronic to chromosome 9 open reading frame 72 (C9ORF72) has recently been identified as the most common genetic cause of both familial and sporadic amyotrophic lateral sclerosis and of f...

Authors: Jennifer S Yokoyama and Howard J Rosen

Stem cell models of Alzheimer's disease and related neurological disorders

Human models of Alzheimer's disease (AD) have the potential to complement existing animal models for carrying out functional studies of AD pathogenesis and the development of novel therapies. An effective huma...

Authors: Frederick J Livesey

Oral curcumin for Alzheimer's disease: tolerability and efficacy in a 24-week randomized, double blind, placebo-controlled study

Curcumin is a polyphenolic compound derived from the plant Curcuma Long Lin that has been demonstrated to have antioxidant and anti-inflammatory effects as well as effects on reducing beta-amyloid aggregation. It...

Authors: John M Ringman, Sally A Frautschy, Edmond Teng, Aynun N Begum, Jenny Bardens, Maryam Beigi, Karen H Gylys, Vladimir Badmaev, Dennis D Heath, Liana G Apostolova, Verna Porter, Zeba Vanek, Gad A Marshall, Gerhard Hellemann, Catherine Sugar, Donna L Masterman…

Potential sources of interference on Abeta immunoassays in biological samples

Therapeutic products that depend on the use of an in vitro diagnostic biomarker test to confirm their effectiveness are increasingly being developed. Use of biomarkers is particularly meaningful in the context of...

Authors: Hugo Vanderstichele, Erik Stoops, Eugeen Vanmechelen and Andreas Jeromin

Neuropsychiatric features of C9orf72-associated behavioral variant frontotemporal dementia and frontotemporal dementia with motor neuron disease

Earlier reports of chromosome 9p-linked frontotemporal dementia (FTD) with amyotrophic lateral sclerosis (ALS) kindreds observed psychosis as a prominent feature in some patients. Since the discovery of chromo...

Authors: Leonel T Takada and Sharon J Sha

C9orf72 immunohistochemistry in Alzheimer's disease

Mutation in chromosome 9 open reading frame 72 (C9orf72) is a major genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), referred to as C9FTD/ALS. The function of the protein is...

Authors: Tibor Hortobágyi

Longitudinal neuroimaging and neuropsychological profiles of frontotemporal dementia with C9ORF72 expansions

Frontotemporal dementia (FTD) is a common cause of early-onset dementia with a significant genetic component, as underlined by the recent identification of repeat expansions in the gene C9ORF72 as a major cause o...

Authors: Colin J Mahoney, Laura E Downey, Gerard R Ridgway, Jon Beck, Shona Clegg, Melanie Blair, Sarah Finnegan, Kelvin K Leung, Tom Yeatman, Hannah Golden, Simon Mead, Jonathan D Rohrer, Nick C Fox and Jason D Warren

Dementia: a global health priority - highlights from an ADI and World Health Organization report

Alzheimer's Disease International is the worldwide federation of Alzheimer associations that represent people with dementia and their families. Alzheimer's Disease International has commissioned a number of Wo...

Authors: Marc Wortmann

Championing of dementia in England

Dementia is starting to attract attention following decades of comparative neglect relative to other disease areas. England has been at the forefront of this sea change as one of the first countries in the wor...

Authors: Zeinab Abdi and Alistair Burns

Alzheimer's disease diagnostic criteria: practical applications

Alzheimer's disease (AD) can be identified prior to the occurrence of dementia by using biomarkers. Three phases of AD are recognized: an asymptomatic biomarker-positive phase, a phase with positive biomarkers...

Authors: Jeffrey Cummings

Apolipoprotein E, amyloid-ß clearance and therapeutic opportunities in Alzheimer's disease

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterised by extracellular amyloid-ß (Aß) and intraneuronal tau protein brain pathologies. The most significant risk factor for non-famil...

Authors: Adam Kline

Pooled-DNA sequencing identifies novel causative variants in PSEN1, GRN and MAPT in a clinical early-onset and familial Alzheimer's disease Ibero-American cohort

Some familial Alzheimer's disease (AD) cases are caused by rare and highly-penetrant mutations in APP, PSEN1, and PSEN2. Mutations in GRN and MAPT, two genes associated with frontotemporal dementia (FTD), have be...

Authors: Sheng Chih Jin, Pau Pastor, Breanna Cooper, Sebastian Cervantes, Bruno A Benitez, Cristina Razquin, Alison Goate and Carlos Cruchaga

Dystrophic neurites express C9orf72 in Alzheimer's disease brains

Chromosome 9 open reading frame 72 (C9orf72) is an evolutionarily conserved protein with unknown function, expressed at high levels in the brain. An expanded hexanucleotide GGGGCC repeat located in the first i...

Authors: Jun-ichi Satoh, Hiroko Tabunoki, Tsuyoshi Ishida, Yuko Saito and Kunimasa Arima

Impaired self-other differentiation in frontotemporal dementia due to the C9ORF72 expansion

An expanded hexanucleotide repeat in the C9ORF72 gene has recently been identified as an important cause of frontotemporal dementia and motor neuron disease; however, the phenotypic spectrum of this entity and it...

Authors: Laura E Downey, Colin J Mahoney, Martin N Rossor, Sebastian J Crutch and Jason D Warren

Con: Alzheimer's disease and circadian dysfunction: chicken or egg?

The development of late-onset Alzheimer's disease is believed to be influenced by genetic, socioeconomic, and lifestyle factors. Recently, converging research in animal and human studies has found that beta-am...

Authors: Abhay Moghekar and Richard J O'Brien

Pro: Alzheimer's disease and circadian dysfunction: chicken or egg?

Alzheimer's disease (AD) is a neurodegenerative disease that accounts for most cases of dementia. Besides progressive cognitive decline, circadian dysfunction is a prominent feature of AD. Circadian disruption...

Authors: Tracy A Bedrosian and Randy J Nelson

Increased expression of the homologue of enhancer-of-split 1 protects neurons from beta amyloid neurotoxicity and hints at an alternative role for transforming growth factor beta1 as a neuroprotector

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the deposition of β-amyloid (Aβ) in the brain, which produces progressive neuronal loss and dementia. We recently demonstrated that the...

Authors: Pedro J Chacón and Alfredo Rodríguez-Tébar

Expanding the genetics of amyotrophic lateral sclerosis and frontotemporal dementia

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized clinically by rapidly progressive paralysis leading ultimately to death from respiratory failure. It is now recognized tha...

Authors: Jennifer C Schymick and Bryan J Traynor

Cognitive and behavioral features of c9FTD/ALS

Numerous kindreds with familial frontotemporal dementia or amyotrophic lateral sclerosis or both have been linked to chromosome 9 (c9FTD/ALS), and an expansion of the GGGGCC hexanucleotide repeat in the non-co...

Authors: Bradley F Boeve and Neill R Graff-Radford

Genetic counseling for FTD/ALS caused by the C9ORF72 hexanucleotide expansion

Frontotemporal degeneration (FTD) and amyotrophic lateral sclerosis (ALS) are related but distinct neurodegenerative diseases. The identification of a hexanucleotide repeat expansion in a noncoding region of t...

Authors: Jamie C Fong, Anna M Karydas and Jill S Goldman

Measuring clinical progression in MCI and pre-MCI populations: enrichment and optimizing clinical outcomes over time

Recent biomarker research has improved the identification of individuals with very early stages of Alzheimer's disease (AD) and has demonstrated that biomarkers are sensitive for measuring progression in the p...

Authors: Suzanne B Hendrix

Systematic reviews on behavioural and psychological symptoms in the older or demented population

Behavioural and psychological symptoms of dementia (BPS) include depressive symptoms, anxiety, apathy, sleep problems, irritability, psychosis, wandering, elation and agitation, and are common in the non-demen...

Authors: Rianne M van der Linde, Blossom CM Stephan, George M Savva, Tom Dening and Carol Brayne

Supporting clinical research in the NHS in England: the National Institute for Health Research Dementias and Neurodegenerative Diseases Research Network

Clinical research is best done when aligned with clinical care - that is, when the patient can be identified, recruited and, in many instances, researched in parallel with the delivery of clinical service. How...

Authors: Piers Kotting, Kris Beicher, Ian G McKeith and Martin N Rossor

Ayurvedic medicinal plants for Alzheimer's disease: a review

Alzheimer's disease is an age-associated, irreversible, progressive neurodegenerative disease that is characterized by severe memory loss, unusual behavior, personality changes, and a decline in cognitive func...

Authors: Rammohan V Rao, Olivier Descamps, Varghese John and Dale E Bredesen

Age-related increase in amyloid plaque burden is associated with impairment in conditioned fear memory in CRND8 mouse model of amyloidosis

The current pathological confirmation of the diagnosis of Alzheimer's disease (AD) is still based on postmortem identification of parenchymal amyloid beta (Aβ) plaques, intra-neuronal neurofibrillary tangles, ...

Authors: Amanda Hanna, Kayleigh Iremonger, Pritam Das, Dennis Dickson, Todd Golde and Christopher Janus

Phenotypic differences between apolipoprotein E genetic subgroups: research and clinical implications

With the recent interest in Alzheimer's disease course modification and earlier, even preclinical, intervention, questions have arisen regarding the potentially confounding impact of apolipoprotein E (APOE) ge...

Authors: Richard J Caselli

Whether, when and how chronic inflammation increases the risk of developing late-onset Alzheimer's disease

Neuropathological studies have revealed the presence of a broad variety of inflammation-related proteins (complement factors, acute-phase proteins, pro-inflammatory cytokines) in Alzheimer's disease (AD) brain...

Authors: Piet Eikelenboom, Jeroen JM Hoozemans, Rob Veerhuis, Eric van Exel, Annemieke JM Rozemuller and Willem A van Gool

Resistant to amyloid-β or just waiting for disease to happen?

The post-mortem finding of abundant intracerebral accumulation of amyloid-β (Aβ) in the cerebral cortex of some people who develop minimal neurofibrillary pathology and remain cognitively intact until death (s...

Authors: Seth Love

Overlapping profiles of Aβ peptides in the Alzheimer's disease and pathological aging brains

A hallmark of Alzheimer's disease (AD) is the presence of senile plaques composed of aggregated amyloid β (Aβ) peptides. Pathological aging (PA) is a postmortem classification that has been used to describe br...

Authors: Brenda D Moore, Paramita Chakrabarty, Yona Levites, Tom L Kukar, Ann-Marie Baine, Tina Moroni, Thomas B Ladd, Pritam Das, Dennis W Dickson and Todd E Golde

Recent Alzheimer's disease research highlights

Authors: Douglas Galasko, Todd Golde and Gordon Wilcock

Factors that influence survival in a probable Alzheimer disease cohort

This longitudinal study examined multiple factors that influence survival in a cohort of Alzheimer patients followed over two decades.

Authors: Susan D Rountree, Wenyaw Chan, Valory N Pavlik, Eveleen J Darby and Rachelle S Doody

Long-term benefit from deep brain stimulation of the subthalamic nucleus: is it for everyone?

Although deep brain stimulation (DBS) has revolutionized our approach to therapy for patients with advanced Parkinson's disease, many questions remain. Should DBS be instituted earlier in the course of the dis...

Authors: Jerrold L Vitek

Examining the mechanisms that link β-amyloid and α-synuclein pathologies

β-amyloid (Aβ) and α-synuclein (α-syn) are aggregation-prone proteins typically associated with two distinct neurodegenerative disorders: Alzheimer's disease (AD) and Parkinson's disease. Yet α-syn was first f...

Authors: Samuel E Marsh and Mathew Blurton-Jones

Reduction of low-density lipoprotein receptor-related protein (LRP1) in hippocampal neurons does not proportionately reduce, or otherwise alter, amyloid deposition in APPswe/PS1dE9 transgenic mice

The low-density lipoprotein receptor-related protein (LRP1) and its family members have been implicated in the pathogenesis of Alzheimer's disease. Multiple susceptibility factors converge to metabolic pathway...

Authors: Guilian Xu, Cameron C Green, Susan E Fromholt and David R Borchelt

Relationships between the amyloid precursor protein and its various proteolytic fragments and neuronal systems

Alzheimer's disease (AD) is a progressive neurodegenerative disease and in its familial form is associated with mutations in the amyloid precursor protein (APP) and the presenilins (PSs). Much data regarding t...

Authors: Sally Hunter and Carol Brayne