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The probabilistic m...
The probabilistic model of Alzheimer disease: the amyloid hypothesis revised
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- Frisoni, G. B. (author)
- Geneva University Hospital,University of Geneva
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- Altomare, D. (author)
- University of Geneva,Geneva University Hospital
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- Thal, D. R. (author)
- University Hospitals Leuven
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- Ribaldi, F. (author)
- Geneva University Hospital,University of Brescia,Centro San Giovanni di Dio Fatebenefratelli,University of Geneva
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- van der Kant, R. (author)
- Vrije Universiteit Amsterdam
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- Ossenkoppele, Rik (author)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Vrije Universiteit Amsterdam
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- Blennow, Kaj, 1958 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry,Sahlgrenska University Hospital
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- Cummings, J. (author)
- University of Nevada, Las Vegas
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- van Duijn, C. (author)
- University of Oxford,Erasmus University Medical Center
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- Nilsson, Peter M. (author)
- Lund University,Lunds universitet,Internmedicin - epidemiologi,Forskargrupper vid Lunds universitet,Internal Medicine - Epidemiology,Lund University Research Groups,Skåne University Hospital
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- Dietrich, P. Y. (author)
- Geneva University Hospital
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- Scheltens, P. (author)
- Vrije Universiteit Amsterdam
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- Dubois, B. (author)
- Paris-Sorbonne University,Brain and Spine Institute (ICM)
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(creator_code:org_t)
- 2021-11-23
- 2022
- English.
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In: Nature Reviews Neuroscience. - : Springer Science and Business Media LLC. - 1471-003X .- 1471-0048. ; 23, s. 53-66
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Abstract
Subject headings
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- The amyloid hypothesis has been the dominant model for the pathogenesis of Alzheimer disease for several decades. In this Perspective, Giovanni Frisoni and colleagues examine evidence for and against this hypothesis before outlining an alternative model, the probabilistic model of Alzheimer disease. The current conceptualization of Alzheimer disease (AD) is driven by the amyloid hypothesis, in which a deterministic chain of events leads from amyloid deposition and then tau deposition to neurodegeneration and progressive cognitive impairment. This model fits autosomal dominant AD but is less applicable to sporadic AD. Owing to emerging information regarding the complex biology of AD and the challenges of developing amyloid-targeting drugs, the amyloid hypothesis needs to be reconsidered. Here we propose a probabilistic model of AD in which three variants of AD (autosomal dominant AD, APOE epsilon 4-related sporadic AD and APOE epsilon 4-unrelated sporadic AD) feature decreasing penetrance and decreasing weight of the amyloid pathophysiological cascade, and increasing weight of stochastic factors (environmental exposures and lower-risk genes). Together, these variants account for a large share of the neuropathological and clinical variability observed in people with AD. The implementation of this model in research might lead to a better understanding of disease pathophysiology, a revision of the current clinical taxonomy and accelerated development of strategies to prevent and treat AD.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- apolipoprotein-e genotype
- posterior cortical atrophy
- a-beta
- genetic
- risk
- neurofibrillary degeneration
- cognitive impairment
- phosphorylated-tau
- apoe genotype
- type-4 allele
- onset
- Neurosciences & Neurology
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Frisoni, G. B.
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Altomare, D.
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Thal, D. R.
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Ribaldi, F.
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van der Kant, R.
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Ossenkoppele, Ri ...
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show more...
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Blennow, Kaj, 19 ...
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Cummings, J.
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van Duijn, C.
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Nilsson, Peter M ...
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Dietrich, P. Y.
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Scheltens, P.
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Dubois, B.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
- Articles in the publication
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Nature Reviews N ...
- By the university
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University of Gothenburg
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Lund University