Paroxysmal slow cortical activity in Alzheimer’s disease and epilepsy is associated with blood-brain barrier dysfunction

2019 ◽  
Vol 11 (521) ◽  
pp. eaaw8954 ◽  
Author(s):  
Dan Z. Milikovsky ◽  
Jonathan Ofer ◽  
Vladimir V. Senatorov ◽  
Aaron R. Friedman ◽  
Ofer Prager ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Causative Role ◽  
Barrier Dysfunction ◽  
Therapeutic Implications ◽  
Young Rats ◽  
Blood Brain ◽  
Nonconvulsive Seizures

A growing body of evidence shows that epileptic activity is frequent but often undiagnosed in patients with Alzheimer’s disease (AD) and has major therapeutic implications. Here, we analyzed electroencephalogram (EEG) data from patients with AD and found an EEG signature of transient slowing of the cortical network that we termed paroxysmal slow wave events (PSWEs). The occurrence per minute of the PSWEs was correlated with level of cognitive impairment. Interictal (between seizures) PSWEs were also found in patients with epilepsy, localized to cortical regions displaying blood-brain barrier (BBB) dysfunction, and in three rodent models with BBB pathology: aged mice, young 5x familial AD model, and status epilepticus–induced epilepsy in young rats. To investigate the potential causative role of BBB dysfunction in network modifications underlying PSWEs, we infused the serum protein albumin directly into the cerebral ventricles of naïve young rats. Infusion of albumin, but not artificial cerebrospinal fluid control, resulted in high incidence of PSWEs. Our results identify PSWEs as an EEG manifestation of nonconvulsive seizures in patients with AD and suggest BBB pathology as an underlying mechanism and as a promising therapeutic target.

scholarly journals Relationship Between Amyloid-β Deposition and Blood–Brain Barrier Dysfunction in Alzheimer’s Disease

2021 ◽  
Vol 15 ◽  
Author(s):  
Dong Wang ◽  
Fanglian Chen ◽  
Zhaoli Han ◽  
Zhenyu Yin ◽  
Xintong Ge ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Brain Barrier ◽  
Amyloid Β ◽  
Brain Barrier ◽  
Barrier Dysfunction ◽  
Factors Affecting ◽  
Blood Brain ◽  
Normal Metabolism

Amyloid-β (Aβ) is the predominant pathologic protein in Alzheimer’s disease (AD). The production and deposition of Aβ are important factors affecting AD progression and prognosis. The deposition of neurotoxic Aβ contributes to damage of the blood–brain barrier. However, the BBB is also crucial in maintaining the normal metabolism of Aβ, and dysfunction of the BBB aggravates Aβ deposition. This review characterizes Aβ deposition and BBB damage in AD, summarizes their interactions, and details their respective mechanisms.

scholarly journals Alzheimer’s disease: A matter of blood–brain barrier dysfunction?

2017 ◽  
Vol 214 (11) ◽  
pp. 3151-3169 ◽  
Author(s):  
Axel Montagne ◽  
Zhen Zhao ◽  
Berislav V. Zlokovic
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Brain Barrier ◽  
Amyloid Β ◽  
Brain Barrier ◽  
Barrier Dysfunction ◽  
Neurodegenerative Process ◽  
Blood Brain ◽  
Underlying Mechanisms

The blood–brain barrier (BBB) keeps neurotoxic plasma-derived components, cells, and pathogens out of the brain. An early BBB breakdown and/or dysfunction have been shown in Alzheimer’s disease (AD) before dementia, neurodegeneration and/or brain atrophy occur. However, the role of BBB breakdown in neurodegenerative disorders is still not fully understood. Here, we examine BBB breakdown in animal models frequently used to study the pathophysiology of AD, including transgenic mice expressing human amyloid-β precursor protein, presenilin 1, and tau mutations, and apolipoprotein E, the strongest genetic risk factor for AD. We discuss the role of BBB breakdown and dysfunction in neurodegenerative process, pitfalls in BBB measurements, and how targeting the BBB can influence the course of neurological disorder. Finally, we comment on future approaches and models to better define, at the cellular and molecular level, the underlying mechanisms between BBB breakdown and neurodegeneration as a basis for developing new therapies for BBB repair to control neurodegeneration.

scholarly journals The Roles of the Microbiome in Alzheimer’s Disease

2021 ◽  
Vol 2 (1) ◽  
pp. 159-167
Author(s):  
Zahin Hafiz ◽  
Moina Malek ◽  
William Ju
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Brain Barrier ◽  
Metabolic Diseases ◽  
The Other ◽  
Therapeutic Interventions ◽  
Brain Barrier ◽  
Therapeutic Implications ◽  
Blood Brain ◽  
The Brain

The gut and the brain are in constant communication in a complex network known as the brain-gut axis. A growing body of research has found links between the brain-gut axis and Alzheimer’s Disease (AD). In this review, we will explore how the mammalian microbiome affects neuroinflammation and increases the permeability of the blood brain barrier in the context of AD. Research shows that the microbiome is associated with neuroinflammation in AD, which is presumably caused by the secretion of cytokines from specialized cells of the brain - microglia and astrocytes. On the other hand, metabolic diseases, caused by microbiota dysbiosis, can increase the permeability of the blood brain barrier. In addition, its higher permeability can allow blood plasma components to enter brain tissue and further develop AD pathology. Findings of the current research have tremendous therapeutic implications. Researchers have speculated whether the therapeutic modification of gut microbiota, through the use of antibiotics and probiotics, may show improvement in AD patients. Our understanding of the pathways and mechanisms involved in the brain-gut axis and AD is still very limited and requires further research before clinical and therapeutic interventions can occur.

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