The probabilistic model of Alzheimer disease
| Autor: | Cornelia M. van Duijn, Philip Scheltens, Bruno Dubois, Jeffrey L. Cummings, Peter M. Nilsson, Rik Ossenkoppele, Rik van der Kant, Giovanni B. Frisoni, Pierre-Yves Dietrich, Daniele Altomare, Kaj Blennow, Dietmar Rudolf Thal, Federica Ribaldi |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Apolipoprotein E
Amyloid tau Proteins GENETIC RISK Disease Amyloid Neuropathies Article Alzheimer Disease NEUROFIBRILLARY DEGENERATION medicine Animals Humans POSTERIOR CORTICAL ATROPHY Cognitive impairment A-BETA TYPE-4 ALLELE Amyloid beta-Peptides Models Statistical Science & Technology APOE GENOTYPE business.industry General Neuroscience Neurodegeneration Neurosciences APOLIPOPROTEIN-E GENOTYPE COGNITIVE IMPAIRMENT medicine.disease Penetrance Biochemistry of Alzheimer's disease ONSET Neurosciences & Neurology Alzheimer's disease business Life Sciences & Biomedicine Neuroscience PHOSPHORYLATED-TAU |
| Zdroj: | Frisoni, G B, Altomare, D, Thal, D R, Ribaldi, F, van der Kant, R, Ossenkoppele, R, Blennow, K, Cummings, J, van Duijn, C, Nilsson, P M, Dietrich, P Y, Scheltens, P & Dubois, B 2022, ' The probabilistic model of Alzheimer disease: the amyloid hypothesis revised ', Nature Reviews Neuroscience, vol. 23, no. 1, pp. 53-66 . https://doi.org/10.1038/s41583-021-00533-w Frisoni, G B, Altomare, D, Thal, D R, Ribaldi, F, van der Kant, R, Ossenkoppele, R, Blennow, K, Cummings, J, van Duijn, C, Nilsson, P M, Dietrich, P-Y, Scheltens, P & Dubois, B 2022, ' The probabilistic model of Alzheimer disease : the amyloid hypothesis revised ', Nature Reviews Neuroscience, vol. 23, no. 1, pp. 53-66 . https://doi.org/10.1038/s41583-021-00533-w Nat Rev Neurosci |
| ISSN: | 1471-003X |
| DOI: | 10.1038/s41583-021-00533-w |
| Popis: | 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 e4-related sporadic AD and APOE e4-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. 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. |
| Databáze: | OpenAIRE |
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