scholarly journals Water exchange rate across the blood‐brain barrier is associated with CSF amyloid‐β 42 in healthy older adults

2021 ◽  
Author(s):  
Brian T. Gold ◽  
Xingfeng Shao ◽  
Tiffany L. Sudduth ◽  
Gregory A. Jicha ◽  
Donna M. Wilcock ◽  
...  
Keyword(s):  
Older Adults ◽  
Exchange Rate ◽  
Blood Brain Barrier ◽  
Water Exchange ◽  
Amyloid Β ◽  
Brain Barrier ◽  
Water Exchange Rate ◽  
Healthy Older Adults ◽  
Blood Brain

scholarly journals Increase in blood–brain barrier leakage in healthy, older adults

GeroScience ◽  
2020 ◽  
Vol 42 (4) ◽  
pp. 1183-1193 ◽  
Author(s):  
Inge C. M. Verheggen ◽  
Joost J. A. de Jong ◽  
Martin P. J. van Boxtel ◽  
Ed H. B. M. Gronenschild ◽  
Walter M. Palm ◽  
...  
Keyword(s):  
Older Adults ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Healthy Older Adults ◽  
Blood Brain

scholarly journals Blood-Brain Barrier Disruption Increases Amyloid-Related Pathology in TgSwDI Mice

2021 ◽  
Vol 22 (3) ◽  
pp. 1231
Author(s):  
Ihab M. Abdallah ◽  
Kamal M. Al-Shami ◽  
Euitaek Yang ◽  
Amal Kaddoumi
Keyword(s):  
Mouse Model ◽  
Blood Brain Barrier ◽  
High Throughput Screening ◽  
Amyloid Β ◽  
Brain Barrier ◽  
Amyloid Angiopathy ◽  
Cancer Resistance ◽  
Screening Assay ◽  
Blood Brain ◽  
High Throughput Screening Assay

In Alzheimer’s disease (AD), several studies have reported blood-brain barrier (BBB) breakdown with compromised function. P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are transport proteins localized at the BBB luminal membrane and play an important role in the clearance of amyloid-β (Aβ). The purpose of this study was to investigate the effect of pharmacological inhibition of Aβ efflux transporters on BBB function and Aβ accumulation and related pathology. Recently, we have developed an in vitro high-throughput screening assay to screen for compounds that modulate the integrity of a cell-based BBB model, which identified elacridar as a disruptor of the monolayer integrity. Elacridar, an investigational compound known for its P-gp and BCRP inhibitory effect and widely used in cancer research. Therefore, it was used as a model compound for further evaluation in a mouse model of AD, namely TgSwDI. TgSwDI mouse is also used as a model for cerebral amyloid angiopathy (CAA). Results showed that P-gp and BCRP inhibition by elacridar disrupted the BBB integrity as measured by increased IgG extravasation and reduced expression of tight junction proteins, increased amyloid deposition due to P-gp, and BCRP downregulation and receptor for advanced glycation end products (RAGE) upregulation, increased CAA and astrogliosis. Further studies revealed the effect was mediated by activation of NF-κB pathway. In conclusion, results suggest that BBB disruption by inhibiting P-gp and BCRP exacerbates AD pathology in a mouse model of AD, and indicate that therapeutic drugs that inhibit P-gp and BCRP could increase the risk for AD.

scholarly journals Increased cerebral vascularization and decreased water exchange across the blood-brain barrier in aquaporin-4 knockout mice

PLoS ONE ◽  
2019 ◽  
Vol 14 (6) ◽  
pp. e0218415 ◽  
Author(s):  
Yifan Zhang ◽  
Kui Xu ◽  
Yuchi Liu ◽  
Bernadette O. Erokwu ◽  
Pan Zhao ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Knockout Mice ◽  
Water Exchange ◽  
Aquaporin 4 ◽  
Brain Barrier ◽  
Blood Brain

P4-069: Modeling amyloid β-peptide transport across the blood-brain barrier in TR-BBB cells

2006 ◽  
Vol 2 ◽  
pp. S533-S534
Author(s):  
Kaoru Yamada ◽  
Chiori Yabuki ◽  
Masanori Tachikawa ◽  
Sumio Ohtsuki ◽  
Dudley K. Strickland ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Amyloid Β ◽  
Brain Barrier ◽  
Peptide Transport ◽  
Amyloid Β Peptide ◽  
Blood Brain

scholarly journals Modulation of γ-Secretase Activity by a Carborane-Based Flurbiprofen Analogue

Molecules ◽  
2021 ◽  
Vol 26 (10) ◽  
pp. 2843
Author(s):  
Stefan Saretz ◽  
Gabriele Basset ◽  
Liridona Useini ◽  
Markus Laube ◽  
Jens Pietzsch ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Pharmaceutical Research ◽  
Amyloid Β ◽  
Brain Barrier ◽  
Blood Brain ◽  
Secretase Activity ◽  
Number Of Patients ◽  
Aging Populations ◽  
A Cell

All over the world, societies are facing rapidly aging populations combined with a growing number of patients suffering from Alzheimer’s disease (AD). One focus in pharmaceutical research to address this issue is on the reduction of the longer amyloid-β (Aβ) fragments in the brain by modulation of γ-secretase, a membrane-bound protease. R-Flurbiprofen (tarenflurbil) was studied in this regard but failed to show significant improvement in AD patients in a phase 3 clinical trial. This was mainly attributed to its low ability to cross the blood–brain barrier (BBB). Here, we present the synthesis and in vitro evaluation of a racemic meta-carborane analogue of flurbiprofen. By introducing the carborane moiety, the hydrophobicity could be shifted into a more favourable range for the penetration of the blood–brain barrier, evident by a logD7.4 value of 2.0. Furthermore, our analogue retained γ-secretase modulator activity in comparison to racemic flurbiprofen in a cell-based assay. These findings demonstrate the potential of carboranes as phenyl mimetics also in AD research.

Blood-brain barrier breakdown, neuroinflammation, and cognitive decline in older adults

2018 ◽  
Vol 14 (12) ◽  
pp. 1640-1650 ◽  
Author(s):  
Gene L. Bowman ◽  
Loïc Dayon ◽  
Richard Kirkland ◽  
Jérôme Wojcik ◽  
Gwendoline Peyratout ◽  
...  
Keyword(s):  
Older Adults ◽  
Cognitive Decline ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Blood Brain ◽  
Barrier Breakdown ◽  
Blood Brain Barrier Breakdown

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 Crocus sativusExtract Tightens the Blood-Brain Barrier, Reduces Amyloid β Load and Related Toxicity in 5XFAD Mice

2017 ◽  
Vol 8 (8) ◽  
pp. 1756-1766 ◽  
Author(s):  
Yazan S. Batarseh ◽  
Sonali S. Bharate ◽  
Vikas Kumar ◽  
Ajay Kumar ◽  
Ram A. Vishwakarma ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Amyloid Β ◽  
Brain Barrier ◽  
Blood Brain ◽  
5Xfad Mice
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