Neuronal activity regulates the regional vulnerability to amyloid-β deposition

By Adam W. Bero, Ping Yan, J. Roh, John R. Cirrito, F. Stewart, Marcus E. Raichle, J. Lee, D. Holtzman. Nature Neuroscience, 2011

894 citations recorded by the source corpus.

Amyloid-β (Aβ) plaque deposition in specific brain regions is a pathological hallmark of Alzheimer's disease. However, the mechanism underlying the regional vulnerability to Aβ deposition in Alzheimer's disease is unknown. Herein, we provide evidence that endogenous neuronal activity regulates the regional concentration of interstitial fluid (ISF) Aβ, which drives local Aβ aggregation. Using in vivo microdialysis, we show that ISF Aβ concentrations in several brain regions of APP transgenic mice before plaque deposition were commensurate with the degree of subsequent plaque deposition and with the concentration of lactate, a marker of neuronal activity. Furthermore, unilateral vibrissal stimulation increased ISF Aβ, and unilateral vibrissal deprivation decreased ISF Aβ and lactate, in contralateral barrel cortex. Long-term unilateral vibrissal deprivation decreased amyloid plaque formation and growth. Our results suggest a mechanism to account for the vulnerability of specific brain regions to Aβ deposition in Alzheimer's disease.

Subfields: Cellular and Molecular Neuroscience, Physiology, Psychiatry and Mental health

View Paper: https://www.semanticscholar.org/paper/5057cdd8e0cafd6a88d760a429885b50bb5c2687

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Citations in the corpus

Alzheimer Disease: An Update on Pathobiology and Treatment Strategies (2019, positive): “sleep is another mechanism Increased synaptic and network activity has been previously shown to stimulate release of extracellular Aβ and tau from neurons (Bero et al., 2011; Brody et al., 2008; Cirrito et al., 2005; Yamada et al., 2014).”
APOE4 Causes Widespread Molecular and Cellular Alterations Associated with Alzheimer’s Disease Phenotypes in Human iPSC-Derived Brain Cell Types (2018, positive): “Increased synaptic activity has been shown to correlate with increased A b production (Bero et al., 2011; Das et al., 2013).”
A Paravascular Pathway Facilitates CSF Flow Through the Brain Parenchyma and the Clearance of Interstitial Solutes, Including Amyloid β (2012, background): “AQP4 facilitates the para-vascular clearance of interstitial amyloid b Soluble amyloid b (Ab) is present in the interstitium of the healthy young brain, yet interstitial Ab levels are correlated with amyloid plaque burden (18).”
Sleep quality and preclinical Alzheimer Disease (2013, neutral): “Brain regions with the highest soluble A levels are also those most prone to amyloid plaques.(36) Notably, the brain regions in the default mode network(37) are those that demonstrate the most activity during quiet wakefulness and are the same areas with the most amyloid deposition during the develo”
β-Amyloid accumulation in the human brain after one night of sleep deprivation (2018, background): “Alternatively, Aβ increases in the hippocampus after SD could reflect increases in Aβ synthesis associated with endogenous neuronal activity during SD (35), or sleep-related changes in hippocampal neurogenesis (36, 37).”
Meditation experience is associated with differences in default mode network activity and connectivity (2011, background): “Sustained neuronal activity has recently been linked to increased amyloid-β deposition (51).”
Activity Dependent Degeneration Explains Hub Vulnerability in Alzheimer's Disease (2012, background): “In addition to the presumed role of disinhibition mentioned in the previous paragraph, a prominent role of excessive neuronal activity in AD pathogenesis has been suggested before: several studies have demonstrated a direct link between neuronal activity and the development of amyloid plaques in tra”