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Margaret Lock
Editions
Hardcover
31.95
25.00
ISBN
9780691149783
328 pp.
6 x 9 1/4
12 line illus.
Paperback
24.95
20.00
ISBN
9780691168470
328 pp.
6 x 9 1/4
12 line illus.
E-book
ISBN
9781400848461
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Due to rapidly aging populations, the number of people worldwide experiencing dementia is increasing, and the projections are grim. Despite billions of dollars invested in medical research, no effective treatment has been discovered for Alzheimer's disease, the most common form of dementia. exposes the predicaments embedded in current efforts to slow down or halt Alzheimer’s disease through early detection of pre-symptomatic biological changes in healthy individuals.Based on a meticulous account of the history of Alzheimer’s disease and extensive in-depth interviews, Margaret Lock highlights the limitations and the dissent associated with biomarker detection. Lock argues that basic research must continue, but should be complemented by a public health approach to prevention that is economically feasible, more humane, and much more effective globally than one exclusively focused on an increasingly harried search for a cure.

is the Marjorie Bronfman Professor Emerita in the Department of Social Studies of Medicine and the Department of Anthropology at McGill University.

More about this book

Shortlisted for the 2014 Mavis Gallant Prize for Non-Fiction, Quebec Writers' Federation
Resources
Chapter 1 [PDF]

Reviews

"[T]houghtful . . . convincing. . . . Margaret Lock is an extremely sharp critic of the Alzheimer's scene."
"[A] diligent survey of research, literature, conferences, and interviews. . . . Lock proves that the science of the disease is just as compelling as poignant accounts from caregivers and those suffering from Alzheimer's disease. Lock highlights just how much we don't know, from problems with Alzheimer's pathology, testing, and diagnosis to the search for a drug treatment. . . . While science plugs away at solving the Alzheimer's conundrum, Lock's call for improved care and social support takes on a new urgency."
"[Lock] delivers key concepts in epidemiology, neuroscience and genetics in a way that is both scholarly and free of unnecessary technical details. Lock's bird's-eye view and mix of diverging sources of information is refreshing. . . . For its wide scope and balanced critical evaluation, is an inspiring read for everyone working in the field."
"Comprehensive, cogent, and densely detailed, provides a useful antidote to media hype about 'silver bullets' that are 'just around the corner' and makes an important contribution to our understanding of an achingly tragic disease that touches virtually all of us."
" is a welcome addition to a body of work that has so productively explored the historical contingencies, cultural specificities, and philosophical dilemmas that surround and shape bodies and people's understandings and inhabitances of them."
" is a gem for young scientists and medical students, and it will challenge them to step back from traditional models, standardised diagnostic procedures and disease specificity to adopt a broader philosophical approach: when is a disease not a disease? . . . Lock's rigorous unpacking of research studies and refusal to accept statements and conclusions from research papers at face value result in a thorough and honest appraisal of the current state of the field. It will be a great help in understanding the confusion and conflicting evidence surrounding this highly important topic."
"Lock's empirical account is a very welcome addition to the literature on biomedical uncertainty."
"[W]hether medical researchers or the general reader, this is a meaningful reading."
" is an engaging read that, while quite granular in its detail, is never dry. . . . Lock clearly summarizes, synthesizes, and critiques the results from research in molecular biology, genetics, neuroimaging, and epidemiology."
" is an eloquently reasoned, provocative work."
"The strength of this book is the in-depth detailing of the limitations of the existing science of Alzheimer's. . . . This book is particularly relevant for researchers in the field of dementia: for those coming from a bio-medical perspective it may help them to be more reflexive about the choices they make in their studies, and for social scientists it may help to further understandings of and potential links with more medically focused research."
"Lock's book is balanced, brilliant, and inspirational. . . . The sheer travel, research, and organization that went into its creation are beyond impressive. Its lasting contribution is to leave the thoughtful reader in the AD field pondering the notion of a conundrum--after all, riddles abound in many aspects of our lives, always pointing to uncertainty."
" is a provocative account of why Alzheimer's disease (AD) is such a puzzling mix of scientific hypotheses, research agendas, pharmaceutical interests, funding objectives, and theories of aging. . . . A timely critique of the disease model and its cultural consequences. The book’s appeal is that it takes readers beyond scientific fields to consider social, historical, and cross-cultural dimensions of AD that broaden conceptual debates about mind and body, nature and nurture, and normal and pathological."
"Lock's book is both a timely and incisive analysis of the dynamics of research, practice and policy in the domain of dementia, and a polemic about how this dynamic affects people living with dementia, and ultimately the way we engage with and manage aging processes as a society."
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Endorsements

"Bringing together an anthropology of predictive medicine with a social study of science, and discussing recent biological discoveries as well as crucial public health problems, offers an insightful approach to the uncertain boundaries between aging and dementia, and brilliantly revisits the philosophical theme of the normal and pathological. Evocatively written, it is a major contribution to the understanding of one of the most perplexing and tragic issues of our time."
" is a must-read for all who are interested in how society and researchers frame the investigation of Alzheimer's disease and its effects on the aging global population. Lock has woven the individual threads of the scientific discussion and debate about dementia into a magnificent tapestry, prompting us to question our assumptions and perceptions. A compelling book."
" is an eye-opening analysis of the tangles of diagnoses and treatments for Alzheimer's as they are experienced by clinicians, researchers, patients, and their families. Lock's nuanced exploration of the risk and uncertainty surrounding genetic knowledge about the brain brings the anthropology of medicine and science to an entirely new and unsurpassed level."
"A riveting plunge into the genomics and neuroscientific epidemiology of this much-feared disease, Margaret Lock's convincingly shows why scientists are unlikely to untangle the causes of Alzheimer's disease anytime soon. This superb contribution to science studies exposes the existential dilemma we all confront: what will our globalized societies do to care for our rapidly aging populations?"
"This book is an excellent treatment of the intricacies of Alzheimer's disease—what it is, what it isn't, what it might be—and deals with its genetic, diagnostic, and predictive uncertainties. In thoroughly exploring the current state of Alzheimer's, the book sheds light on what makes most diseases complex."
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Spanish Sentences Maker sentimiento (lang: sp)
No seas tan insustancial, pon sentimiento en lo que haces.
Don't be so blasé, put feeling into what you do.
En mi país hay un sentimiento nacionalista muy fuerte.
In my country there is a strong nationalistic sentiment.
La guerra de Afganistán había llevado a un sentimiento general de descontento.
The war in Afganistan had caused a general feeling of discontent.
De ahí nuestro sentimiento.
Which is why we feel as we do.
Puedo entender el sentimiento.
I can understand the sentiment.
Ese sentimiento ya no tiene cabida.
There must be no more of this.
Acompañamos a su familia en el sentimiento.
Our thoughts and prayers are with his family at this time.
Puede ser un sentimiento de culpabilidad.
The reason could of course be a guilty conscience.
Es un sentimiento común a todos los mamíferos.
It is a feeling which all mammals have in common.
Ese sentimiento seguramente no existe y debemos lamentarlo.
That is not really the impression they have, and we should regret this.
Hay muchos puntos en los que estamos de acuerdo con el sentimiento general de este informe, con el sentimiento de urgencia, con el sentimiento de necesidad política.
There are many points on which we agree with the general feeling of this report, with the feeling of urgency, with the feeling of political necessity.
Estoy completamente de acuerdo con este sentimiento político.
I fully agree with this political sentiment.
Por ello siempre la recordaremos con un sentimiento de gratitud.
We will also forever associate it with a sense of gratitude.
¿Quizás exista un sentimiento de culpabilidad frente a los candidatos rezagados?
Could this be a case, perhaps, of misplaced guilt in respect of the candidates left behind?
Este sentimiento no lo comparten los ciudadanos de la Unión.
This feeling is not present among Union citizens.
Está claro que la Asamblea comparte plenamente este sentimiento.
Clearly the House is fully in agreement with that sentiment.
Creo que debemos decirlo con un sentimiento de gratitud.
I think we should note this with a sense of gratitude.
Sinceramente no descubro ningún sentimiento europeo en esta cuestión.
I certainly have no European sentiment in this matter.
El informe Sterckx nos deja, en definitiva, un curioso sentimiento.
In the final analysis, therefore, the Sterckx report leaves a strange feeling.
Nosotros observamos esto con un sentimiento de solidaridad.
We look on this with solidarity.
Este sentimiento debe nacer de abajo y no de arriba.
This sentiment must originate from the bottom and not the top.
Eso no disminuye nuestro sentimiento de gratitud hacia ustedes.
That does not diminish our sense of gratitude towards you.
Diría incluso que existe un sentimiento de desesperación.
I would even say that there is even a sense of despair.
Eso demuestra que aún pervive el agresivo sentimiento antipolaco.
This proves that aggressive anti-Polish sentiment still persists.
Que ese sentimiento sea injusto es otra cosa.
Whether or not this feeling is unfair is irrelevant.
Pero falta el sentimiento global, así como el propio compromiso.
But the overall feeling is missing, and the commitment itself is missing.
Ello ha inspirado un nuevo sentimiento de solidaridad en China.
That inspired a new sense of solidarity in China.
Detesto el sentimiento general antiestadounidense que se respira aquí.
I detest the general anti-Americanism of this place.
Son la expresión de un sentimiento comunitario de sus ciudadanos.
They are an expression of the feeling of community felt by its citizens.
Lamentablemente, en esta Cámara, hay muchos ejemplos de sentimiento antiamericano.
Sadly, in this House there are many examples of anti-American sentiment.
Lo lamentamos y acompañamos en el sentimiento a sus familias.
We deplore it, and our thoughts are with their families.
¿Cómo ha cambiado el sentimiento general con respecto a la UE?
How has the general feeling towards the EU changed?
Lo que ven son "desigualdades, un sentimiento de injusticia, inseguridad".
What they see are 'inequalities, a feeling of injustice, insecurity'.
Estoy seguro de que toda la Asamblea comparte su sentimiento.
I am sure the whole house shares your feelings.
Este es el sentimiento y el deber de esta Comisión.
That is the feeling and duty of the Commission.
Transmitiré este sentimiento unánime a la Sra. Díez de Rivera.
I shall pass on these unanimous sentiments to Mrs Díez de Rivera.
Espero, señor Lamy, que suscriba ese sentimiento tan importante.
I hope, Mr Lamy, that you will subscribe to that very important sentiment.
Insistamos, no obstante, en que, si miramos al pasado, nuestro sentimiento tiene que ser de satisfacción, y felizmente, si miramos al futuro, nuestro sentimiento puede ser de esperanza.
Let us emphasise, however, that, looking back at the past, we must feel pleased and that, happily, looking into the future, we can feel hopeful.
Este es un sentimiento que los hombres nunca tendrán y una diferencia importante.
This is a feeling which men will never have and it is an important difference.
Diremos más bien que la degeneración del sentimiento religioso puede llevar a la xenofobia.
On the contrary, xenophobia is more likely to be caused by a decline in religious convictions.
Los ciudadanos de Europa no se sienten europeos y ese sentimiento no va a cambiar con rapidez.
Indeed, the citizens of Europe do not feel European and this will not change overnight.
Al leer el informe y escuchar el debate, tengo un fuerte sentimiento de déjà vu.
When I read the report and hear the discussions, I get a strong feeling of déjà vu.
Tenemos una gran indignación moral y, a la vez, un gran sentimiento de impotencia.
We stand here in moral indignation and are, at the same time, filled with a huge sense of powerlessness.
Refuerza el sentimiento de pertenecer a la Unión Europea identificando raíces que nos son comunes.
It strengthens the sense of belonging to the European Union by identifying the roots we all share.
Tampoco debe de ser confundida con una especie de sentimiento anti-europeo.
Neither should it be confused with a kind of anti-European sentiment.
Señor Balfe, como grupo de uno, sé que ese sentimiento suyo es unánime.
Mr Balfe, as a group of one, I am sure you are unanimous on that sentiment.
Esto hiere mi sentimiento nacional y mi sentido de la historia.
It offends my national sentiment and feeling for history.
Desde entonces se ha logrado mucho, pero ahora me invade más y más un sentimiento incómodo.
A great deal was subsequently achieved, but I am now increasingly feeling uncomfortable.
Dota a Europa de sentimiento y de un alma, como acaba de señalarse aquí.
As mentioned a moment ago, it will inject feeling and soul into Europe.
Los ciudadanos de la Unión se sentirán también fortalecidos en su sentimiento de seguridad.
The EU's citizens will also feel their sense of security reinforced.
Yo no comparto la opinión de que la Unión Europea no tiene peso ninguno, ese sentimiento de autofrustración.
I do not share the frustrating feeling that the European Union carries no weight.
Lo que resulta decisivo para el sentimiento público de pertenencia es lo que le gusta.
What is decisive for the public's sense of belonging is what goes down well with them.
Hay una posibilidad de que esto pueda cambiar en 2006, dependiendo del sentimiento nacional.
There is a possibility that this may change in 2006, depending on national feeling.

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The lipid bilayer's permeability to molecules such as TGLs and possibly drugs can be increased by the formation of the TO aggregate. This is demonstrated by the higher flip-flop rate of TO in the 5.2% simulations, in which the aggregate is present. Furthermore, one or two beads of water could be seen in the aggregate in the 16X5 simulations. Neutral lipid probes used for fluorescence, such as the environment-sensitive probe Laurdan, or the Electron Paramagnetic Resonance (EPR) probe methyl-5-doxylstearic acid spin-label (Me-5-DSA); which are normally presumed to reside at the membrane interface, can be similarly induced to partition into the bilayer center by a high concentration of TGLs. If the probes do partition into the disordered, isotropic TO aggregate at the bilayer center, they will report a more fluid and isotropic environment than at the bilayer interface. The lower order and high hydration properties in 5% TO-incorporated POPC membranes, as detected by Laurdan General Polarization and EPR experiments [30] , is readily explained by such anomalous probe partitioning. When a lower amount of TO is incorporated in the bilayer, both Laurdan and the EPR probes detect an ordered environment typical of a bilayer interface [30] .

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, [56] . Being more hydrophobic, TGLs will flip-flop at even higher rates as seen in the simulations. 2.3% TGL in POPC does not have a significant impact on structure or dynamics of the membrane. The interfacial fraction of TGLs in all our simulations have the β-glycerol bead less hydrated than the two α-glycerol beads, in very good agreement with 13 C-NMR data.

In summary, the simulations reported here provide evidence for the formation of stable, disordered, isotropic, mobile triolein aggregates at the center of a planar lipid bilayer, at concentrations ∼5% TO. In biological systems, similar aggregates, but of a larger size, can be observed in activated or malignant mammalian cells which contain high amounts of TGLs, and in ER membranes where TGLs are synthesized. Our work therefore provides credence to the existence of the “mobile lipid domain” rich in TGLs, residing in activated cells, and to the theory that lipid droplets are indeed synthesized in the ER. Such aggregates will give the membrane a blister-like appearance, and destabilize the formation of multilamellar phases in model membranes, and perhaps even in living cell organelles like lysosomes. The partitioning free energy of neutral lipid molecules and lipid probes will be lowered by the aggregate, and might result in anomalous probe partitioning into the bilayer center, which should be taken into account when interpreting fluorescence, EPR, or other probe-related measurements. The experimental evidence of TGL aggregates such as those seen in our simulations comes mainly from TEM images of freeze fractured activated cells, from the 1 H-NMR mobile lipid signal obtained from live cells, from EM images of the ER membrane, and the isotropic environment detected by EPR and Laurdan GP in POPC membranes containing 5% TO [30] . If TGL-like oils can indeed be accommodated at the bilayer center, as shown by our data, then the solubility levels of TGLs in planar lipid bilayers are higher than earlier reported.

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