P3-247: Leptomeningeal Blood-Brain Barrier Leakage is Associated with Cerebrovascular Damage in Mild Cognitive Impairment and Alzheimer’S Disease

2016 ◽  
Vol 12 ◽  
pp. P923-P923
Author(s):  
Whitney M. Freeze ◽  
Roald S. Schnerr ◽  
Jacobus F. Jansen ◽  
Miguel Palm ◽  
Erik I. Hoff ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Blood Brain

scholarly journals Cancer Chemotherapy Related Cognitive Impairment and the Impact of the Alzheimer’s Disease Risk Factor APOE

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3842
Author(s):  
Harvey R. Fernandez ◽  
Ashima Varma ◽  
Sarah A. Flowers ◽  
George William Rebeck
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Cognitive Impairment ◽  
Blood Brain Barrier ◽  
Cancer Chemotherapy ◽  
Apoe Genotype ◽  
Brain Barrier ◽  
Blood Brain

Cancer related cognitive impairment (CRCI) is a serious impairment to maintaining quality of life in cancer survivors. Cancer chemotherapy contributes to this condition through several potential mechanisms, including damage to the blood brain barrier, increases in oxidative stress and inflammation in the brain, and impaired neurogenesis, each of which lead to neuronal dysfunction. A genetic predisposition to CRCI is the E4 allele of the Apolipoprotein E gene (APOE), which is also the strongest genetic risk factor for Alzheimer’s disease. In normal brains, APOE performs essential lipid transport functions. The APOE4 isoform has been linked to altered lipid binding, increased oxidative stress and inflammation, reduced turnover of neural progenitor cells, and impairment of the blood brain barrier. As chemotherapy also affects these processes, the influence of APOE4 on CRCI takes on great significance. This review outlines the main areas where APOE genotype could play a role in CRCI. Potential therapeutics based on APOE biology could mitigate these detrimental cognitive effects for those receiving chemotherapy, emphasizing that the APOE genotype could help in developing personalized cancer treatment regimens.

scholarly journals Inhibition of mTOR protects the blood-brain barrier in models of Alzheimer’s disease and vascular cognitive impairment

2018 ◽  
Vol 314 (4) ◽  
pp. H693-H703 ◽  
Author(s):  
Candice E. Van Skike ◽  
Jordan B. Jahrling ◽  
Angela B. Olson ◽  
Naomi L. Sayre ◽  
Stacy A. Hussong ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Blood Brain Barrier ◽  
Vascular Cognitive Impairment ◽  
Brain Barrier ◽  
Target Of Rapamycin ◽  
Mtor Inhibition ◽  
Mechanistic Target Of Rapamycin ◽  
Blood Brain

An intact blood-brain barrier (BBB) limits entry of proinflammatory and neurotoxic blood-derived factors into the brain parenchyma. The BBB is damaged in Alzheimer’s disease (AD), which contributes significantly to the progression of AD pathologies and cognitive decline. However, the mechanisms underlying BBB breakdown in AD remain elusive, and no interventions are available for treatment or prevention. We and others recently established that inhibition of the mammalian/mechanistic target of rapamycin (mTOR) pathway with rapamycin yields significant neuroprotective effects, improving cerebrovascular and cognitive function in mouse models of AD. To test whether mTOR inhibition protects the BBB in neurological diseases of aging, we treated hAPP(J20) mice modeling AD and low-density lipoprotein receptor-null (LDLR−/−) mice modeling vascular cognitive impairment with rapamycin. We found that inhibition of mTOR abrogates BBB breakdown in hAPP(J20) and LDLR−/− mice. Experiments using an in vitro BBB model indicated that mTOR attenuation preserves BBB integrity through upregulation of specific tight junction proteins and downregulation of matrix metalloproteinase-9 activity. Together, our data establish mTOR activity as a critical mediator of BBB breakdown in AD and, potentially, vascular cognitive impairment and suggest that rapamycin and/or rapalogs could be used for the restoration of BBB integrity. NEW & NOTEWORTHY This report establishes mammalian/mechanistic target of rapamycin as a critical mediator of blood-brain barrier breakdown in models of Alzheimer's disease and vascular cognitive impairment and suggests that drugs targeting the target of rapamycin pathway could be used for the restoration of blood-brain barrier integrity in disease states.

scholarly journals A first-principles study on potential chelation agents and indicators of Alzheimer's disease

RSC Advances ◽  
2020 ◽  
Vol 10 (58) ◽  
pp. 35574-35581
Author(s):  
Bryan Wang ◽  
Xuan Luo
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Human Serum ◽  
Blood Brain Barrier ◽  
First Principles ◽  
Brain Barrier ◽  
Serum Transferrin ◽  
Human Serum Transferrin ◽  
First Principles Study ◽  
Blood Brain

Human-serum transferrin is involved in the transportation of aluminum across the blood–brain barrier.

scholarly journals Probable Causes of Alzheimer’s Disease

Sci ◽  
2021 ◽  
Vol 3 (1) ◽  
pp. 16
Author(s):  
James David Adams
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Lactic Acid ◽  
Blood Brain Barrier ◽  
Transient Receptor Potential ◽  
Brain Barrier ◽  
Folate Intake ◽  
Blood Brain ◽  
Age Related ◽  
The Brain

A three-part mechanism is proposed for the induction of Alzheimer’s disease: (1) decreased blood lactic acid; (2) increased blood ceramide and adipokines; (3) decreased blood folic acid. The age-related nature of these mechanisms comes from age-associated decreased muscle mass, increased visceral fat and changes in diet. This mechanism also explains why many people do not develop Alzheimer’s disease. Simple changes in lifestyle and diet can prevent Alzheimer’s disease. Alzheimer’s disease is caused by a cascade of events that culminates in damage to the blood–brain barrier and damage to neurons. The blood–brain barrier keeps toxic molecules out of the brain and retains essential molecules in the brain. Lactic acid is a nutrient to the brain and is produced by exercise. Damage to endothelial cells and pericytes by inadequate lactic acid leads to blood–brain barrier damage and brain damage. Inadequate folate intake and oxidative stress induced by activation of transient receptor potential cation channels and endothelial nitric oxide synthase damage the blood–brain barrier. NAD depletion due to inadequate intake of nicotinamide and alterations in the kynurenine pathway damages neurons. Changes in microRNA levels may be the terminal events that cause neuronal death leading to Alzheimer’s disease. A new mechanism of Alzheimer’s disease induction is presented involving lactic acid, ceramide, IL-1β, tumor necrosis factor α, folate, nicotinamide, kynurenine metabolites and microRNA.

Recent Advances in Targeted Drug Delivery Approaches using Lipidic and Polymeric Nanocarriers for the management of Alzheimer’s Disease

2021 ◽  
Vol 27 ◽  
Author(s):  
Dhara Lakdawala ◽  
Md Abdur Rashid ◽  
Farhan Jalees Ahmad
Keyword(s):  
Alzheimer’S Disease ◽  
Drug Delivery ◽  
Alzheimer's Disease ◽  
Blood Brain Barrier ◽  
Targeted Drug Delivery ◽  
Brain Barrier ◽  
Polymeric Nanocarriers ◽  
Blood Brain ◽  
Targeted Drug ◽  
The Brain

: Drug delivery to the brain has remained a significant challenge in treating neurodegenerative disorders such as Alzheimer's disease due to the presence of the blood-brain barrier, which primarily obstructs the access of drugs and biomolecules into the brain. Several methods to overcome the blood-brain barrier have been employed, such as chemical disruption, surgical intervention, focused ultrasound, intranasal delivery and using nanocarriers. Nanocarrier systems remain the method of choice and have shown promising results over the past decade to achieve better drug targeting. Polymeric nanocarriers and lipidic nanoparticles act as a carrier system providing better encapsulation of drugs, site-specific delivery, increased bioavailability and sustained release of drugs. The surface modifications and functionalization of these nanocarrier systems have greatly facilitated targeted drug delivery. The safety and efficacy of these nanocarrier systems have been ascertained by several in vitro and in vivo models. In the present review, we have elaborated on recent developments of nanoparticles as a drug delivery system for Alzheimer's disease, explicitly focusing on polymeric and lipidic nanoparticles.

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