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@ARTICLE{Simons:265749,
author = {Simons, Mikael and Levin, Johannes and Dichgans, Martin},
title = {{T}ipping points in neurodegeneration.},
journal = {Neuron},
volume = {111},
number = {19},
issn = {0896-6273},
address = {New York, NY},
publisher = {Elsevier},
reportid = {DZNE-2023-01024},
pages = {2954 - 2968},
year = {2023},
abstract = {In Alzheimer's disease (AD), Aβ deposits form slowly,
several decades before further pathological events trigger
neurodegeneration and dementia. However, a substantial
proportion of affected individuals remains non-demented
despite AD pathology, raising questions about the underlying
factors that determine the transition to clinical disease.
Here, we emphasize the critical function of resilience and
resistance factors, which we extend beyond the concept of
cognitive reserve to include the glial, immune, and vascular
system. We review the evidence and use the metaphor of
'tipping points' to illustrate how gradually forming AD
neuropathology in the preclinical stage can transition to
dementia once adaptive functions of the glial, immune, and
vascular system are lost and self-reinforcing pathological
cascades are unleashed. Thus, we propose an expanded
framework for pathomechanistic research that focuses on
tipping points and non-neuronal resilience mechanisms, which
may represent previously untapped therapeutic targets in
preclinical AD.},
subtyp = {Review Article},
keywords = {Humans / Alzheimer Disease: pathology / Neuroglia:
pathology / Amyloid beta-Peptides / Alzheimer's disease
(Other) / glia (Other) / inflammation (Other) /
neurodegeneration (Other) / vasculature (Other) / Amyloid
beta-Peptides (NLM Chemicals)},
cin = {AG Dichgans / AG Simons / AG Levin / Clinical Research
(Munich)},
ddc = {610},
cid = {I:(DE-2719)5000022 / I:(DE-2719)1110008 /
I:(DE-2719)1111016 / I:(DE-2719)1111015},
pnm = {353 - Clinical and Health Care Research (POF4-353) / 351 -
Brain Function (POF4-351)},
pid = {G:(DE-HGF)POF4-353 / G:(DE-HGF)POF4-351},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37385247},
doi = {10.1016/j.neuron.2023.05.031},
url = {https://pub.dzne.de/record/265749},
}