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000265749 1001_ $$0P:(DE-2719)2811642$$aSimons, Mikael$$b0$$eFirst author$$udzne
000265749 245__ $$aTipping points in neurodegeneration.
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000265749 520__ $$aIn Alzheimer's disease (AD), Aβ deposits form slowly, several decades before further pathological events trigger neurodegeneration and dementia. However, a substantial proportion of affected individuals remains non-demented despite AD pathology, raising questions about the underlying factors that determine the transition to clinical disease. Here, we emphasize the critical function of resilience and resistance factors, which we extend beyond the concept of cognitive reserve to include the glial, immune, and vascular system. We review the evidence and use the metaphor of 'tipping points' to illustrate how gradually forming AD neuropathology in the preclinical stage can transition to dementia once adaptive functions of the glial, immune, and vascular system are lost and self-reinforcing pathological cascades are unleashed. Thus, we propose an expanded framework for pathomechanistic research that focuses on tipping points and non-neuronal resilience mechanisms, which may represent previously untapped therapeutic targets in preclinical AD.
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000265749 650_7 $$2Other$$aAlzheimer's disease
000265749 650_7 $$2Other$$aglia
000265749 650_7 $$2Other$$ainflammation
000265749 650_7 $$2Other$$aneurodegeneration
000265749 650_7 $$2Other$$avasculature
000265749 650_7 $$2NLM Chemicals$$aAmyloid beta-Peptides
000265749 650_2 $$2MeSH$$aHumans
000265749 650_2 $$2MeSH$$aAlzheimer Disease: pathology
000265749 650_2 $$2MeSH$$aNeuroglia: pathology
000265749 650_2 $$2MeSH$$aAmyloid beta-Peptides
000265749 7001_ $$0P:(DE-2719)2811659$$aLevin, Johannes$$b1$$udzne
000265749 7001_ $$0P:(DE-2719)2000030$$aDichgans, Martin$$b2$$eLast author$$udzne
000265749 773__ $$0PERI:(DE-600)2001944-0$$a10.1016/j.neuron.2023.05.031$$gVol. 111, no. 19, p. 2954 - 2968$$n19$$p2954 - 2968$$tNeuron$$v111$$x0896-6273$$y2023
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000265749 9201_ $$0I:(DE-2719)5000022$$kAG Dichgans$$lVascular Cognitive Impairment & Post-Stroke Dementia$$x0
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