Journal Article (Review Article)

DZNE-2023-01024

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Tipping points in neurodegeneration.

Simons, M. (First author)DZNE* ; Levin, J.DZNE* ; Dichgans, M. (Last author)DZNE*

2023
Elsevier New York, NY

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Please use a persistent id in citations: doi:10.1016/j.neuron.2023.05.031

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.

Keyword(s): Humans (MeSH) ; Alzheimer Disease: pathology (MeSH) ; Neuroglia: pathology (MeSH) ; Amyloid beta-Peptides (MeSH) ; Alzheimer's disease ; glia ; inflammation ; neurodegeneration ; vasculature ; Amyloid beta-Peptides

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Contributing Institute(s):

1. Vascular Cognitive Impairment & Post-Stroke Dementia (AG Dichgans)
2. Molecular Neurobiology (AG Simons)
3. Clinical Neurodegeneration (AG Levin)
4. Clinical Research (Munich) (Clinical Research (Munich))

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)
2. 351 - Brain Function (POF4-351) (POF4-351)

Appears in the scientific report 2023

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 15 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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