Naslov
Neurovascular unit, microbleeds, and glymphatic system as convergent determinants of stroke, Alzheimer's disease and idiopathic normotensive hydrocephalus

Autori
Šimić, Goran

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, prošireni sažetak, ostalo

Izvornik
BUSM Pathology & Laboratory Medicine Seminar Series: Fall 2017 ~ Friday, October 27th, 2017 / - , 2017, 1-2

Skup
Boston University School of Medicine Pathology & Laboratory Medicine Seminar Series

Mjesto i datum
Boston (MA), Sjedinjene Američke Države, 27.11.2017

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
neurovascular unit ; Alzheimer's disease ; cerebral microbleeds ; amyloid precursor protein ; amyloid β ; astrocytes ; blood-brain barrier ; cerebrospinal fluid ; innate immunity ; microglia ; monocytes ; stroke mechanisms ; coagulation ; neuroinflammation ; tau proteins ; extracellular matrix

Sažetak
While it is generally considered that stroke occurs only in the context of vascular disease, recent evidence shows that all underlying processes leading to stroke depend on interactions of neurons, glial cells, vascular endothelial cells and pericytes, and components of the extracellular matrix, altogether referred to as the neurovascular unit (NVU), and that recovery after stroke also depends on the interaction of all these structures within the NVU. To understand the spatial, temporal, and cellular aspects of Alzheimer's disease (AD) in a holistic way, the known biochemistry needs to be integrated into the complex concept of neuronal, glial, and synaptic vulnerability of each individual brain. In that sense, AD can be described as a three-stage process. First, a “biochemical phase” of AD is characterized by mainly qualitative changes resulting from changes in amyloid precursor protein (APP) metabolism and proteostatic stress (changes in APP metabolism, Aβ-conformational changes, oligomerization, spreading, aggregation, interactions, increased oxidative stress ; tau conformational and posttranslational changes, oligomerization, spreading, aggregation, interactions, mislocalization) and homeostatic cellular responses to those stresses. Second, a “cellular phase”, in which clearance problems with additional proteostasis dysfunction due to aging cause dysfunction of the blood-brain barrier (BBB) and glymphatic system, non-beneficial (destructive) activation of microglia, astrogliosis with dysfunction in neuronal homeostatic scaling and short- and long-term plasticity, myelin breakdown and disbalance in lipoprotein metabolism, and early cerebrospinal fluid (CSF) alterations. Finally, a “clinical phase”, in which chronic inflammation, circuitry imbalance, and BBB dysruption lead to significant synaptic failure, cell death, and cortical atrophy and dementia. Within this context, it is important to emphasize that continuously excessive vascular fluctuations, such as hypoperfusion and hypoxia, cannot be separated from the rest of the early AD pathological processes, particularly because of inherent vascular problems due to capillary amyloid angiopathy (CAA), which considerably increases the risk for dementia.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti, Kliničke medicinske znanosti, Psihologija, Kognitivna znanost (prirodne, tehničke, biomedicina i zdravstvo, društvene i humanističke znanosti)

Napomena
The Boston University has made a streamline video
of the lecture available to students on a
password-protected site. Audio files are availabe
for download and distribution, external to the
password-protected site.

POVEZANOST RADA