Prof. Costantino Iadecola | The Vascular Biology of Dementia

Gastvortrag

  • Datum: 29.11.2019
  • Uhrzeit: 14:00 - 15:00
  • Vortragende(r): Prof. Costantino Iadecola
  • Anne Parrish Titzell Professor of Neurology; Director and Chair, Weill Cornell Medicine, Feil Family Brain and Mind Research Institute, New York, USA
  • Ort: MPI für Kognitions- und Neurowissenschaften
  • Raum: Wilhelm Wundt Raum (A400)
The brain lacks energy reserves and is vitally dependent on a continuous and well-regulated delivery oxygen and glucose through the cerebral blood supply. Structural and functional alterations of cerebral blood vessels have emerged as a key correlate of conditions associated with cognitive impairment. The concept of “neurovascular unit” (NVU) was introduced in 2001 to highlight the close developmental, structural, and functional interactions between brain cells and cerebral blood vessels, and their coordinated reaction to injury 1. Comprised of neurons, glia, perivascular cells, e.g., perivascular macrophages, and vascular cells (endothelium, smooth muscle cells, and pericytes), the NVU is responsible for matching the delivery of blood to the brain with local energy needs dictated by brain activity. The NVU is also involved in regulating the molecular exchange between blood and brain (blood-brain barrier), clearance of metabolic byproducts through perivascular, paravascular and transvascular routes, trafficking of immune cells, and trophic support to brain cells (matrix, growth factors, etc.). NVU dysfunction, involving not just flow regulation but also other NVU functions, is central to the pathobiology of dementia and alters the homeostasis of the brain microenvironment in regions involved in cognition leading to cognitive impairment. Thus, neurovascular dysfunction is observed not only in vascular cognitive impairment, but also in Alzheimer’s disease, attesting to the significant overlap between these conditions 2. In addition, major risk factors for cognitive impairment, such as hypertension, ApoE4 genotype, and high salt intake, are also associated with neurovascular dysfunction 3-5. Activation of innate immunity, vascular oxidative stress, and inflammation are major pathogenic factors, but the underlying molecular mechanisms and their link to cognitive impairment remain poorly understood. Recent data revealed a previously appreciated link between vascular risk factors and neurodegenerative mediators6, which may have major diagnostic and therapeutic implications for both vascular and neurodegenerative dementias.

References

1. Iadecola C. The Neurovascular Unit Coming of Age: A Journey through Neurovascular Coupling in Health and Disease. Neuron. 2017;96:17–42.

2. Iadecola C. The pathobiology of vascular dementia. Neuron. 2013;80:844–866.

3. Faraco G, Brea D, Garcia-Bonilla L, Wang G, Racchumi G, Chang H, Buendia I, Santisteban MM, Segarra SG, Koizumi K, Sugiyama Y, Murphy M, Voss H, Anrather J, Iadecola C. Dietary salt promotes neurovascular and cognitive dysfunction through a gut-initiated TH17 response. Nat Neurosci. 2018;21:240–249.

4. Koizumi K, Hattori Y, S-J A, Wang G, Buendia I, Ciacciarelli A, Uekawa K, Zhao L, Voss HU, Paul SM, Schaffer CB, Park L, Iadecola C. Apoε4 disrupts neurovascular regulation and undermines white matter integrity and cognitive function. Nat Commun. 2018; 9:3896.

5. Faraco G, Sugiyama Y, Lane D, Garcia-Bonilla L, Chang H, Santisteban MM, Racchumi G, Murphy M, van Rooijen N, Anrather J, Iadecola C. Perivascular macrophages mediate the neurovascular and cognitive dysfunction associated with hypertension. J CLin Invest. 2016;126:4674–4689.

6. Faraco, G, Hochrainer, K., Segarra, S.G., Schaeffer, S., Santisteban, M.M., Menon, A., Jiang, H., Holtzman, D.M., Anrather, J. and Iadecola, C: Dietary salt promotes cognitive impairment through tau phosphorylation. Nature, in press
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