Neuropathological Condition Research Articles

Impaired axon initial segment structure and function in a model of ARHGEF9 developmental and epileptic encephalopathy

Developmental and epileptic encephalopathies (DEE) are rare but devastating and largely intractable childhood epilepsies. Genetic variants in ARHGEF9, encoding a scaffolding protein important for the organization of the postsynaptic density of inhibitory synapses, are associated with DEE accompanied by complex neurological phenotypes. In a mouse model carrying a patient-derived ARHGEF9 variant associated with severe disease, we observed aggregation of postsynaptic proteins and loss of functional inhibitory synapses at the axon initial segment (AIS), altered axo-axonic synaptic inhibition, disrupted action potential generation, and complex seizure phenotypes consistent with clinical observations. These results illustrate diverse roles of ARHGEF9 that converge on regulation of the structure and function of the AIS, thus revealing a pathological mechanism for ARHGEF9-associated DEE. This unique example of a neuropathological condition associated with multiple AIS dysfunctions may inform strategies for treating neurodevelopmental diseases.

An interpretable tinnitus prediction framework using gap-prepulse inhibition in auditory late response and electroencephalogram.

Tinnitus is a neuropathological condition that results in mild buzzing or ringing of the ears without an external sound source. Current tinnitus diagnostic methods often rely on subjective assessment and require intricate medical examinations. This study aimed to propose an interpretable tinnitus diagnostic framework using auditory late response (ALR) and electroencephalogram (EEG), inspired by the gap-prepulse inhibition (GPI) paradigm. We collected spontaneous EEG and ALR data from 44 patients with tinnitus and 47 hearing loss-matched controls using specialized hardware to capture responses to sound stimuli with embedded gaps. In this cohort study of tinnitus and control groups, we examined EEG spectral and ALR features of N-P complexes, comparing the responses to gap durations of 50 and 20 ms alongside no-gap conditions. To this end, we developed an interpretable tinnitus diagnostic model using ALR and EEG metrics, boosting machine learning architecture, and explainable feature attribution approaches. Our proposed model achieved 90 % accuracy in identifying tinnitus, with an area under the performance curve of 0.89. The explainable artificial intelligence approaches have revealed gap-embedded ALR features such as the GPI ratio of N1-P2 and EEG spectral ratio, which can serve as diagnostic metrics for tinnitus. Our method successfully provides personalized prediction explanations for tinnitus diagnosis using gap-embedded auditory and neurological features. Deficits in GPI alongside activity in the EEG alpha-beta ratio offer a promising screening tool for assessing tinnitus risk, aligning with current clinical insights from hearing research.

Alzheimer’s Disease: An Outline of Therapeutic Interventions by different Approaches

A neurodegenerative condition called Alzheimer's disease (AD) impairs neurocognitive function and hinders the growth of mental ability. This neuropathological condition presents with neurodegeneration, neuronal loss, and the development of neurofibrillary tangles and Ab plaques. Dementia, neuronal loss, and the development of neurofibrillary tangles and Ab plaques are the hallmarks of this neuropathological disorder. Such a medication is not able to cure Alzheimer's disease. The drug that's now available just treats symptoms. Two major obstacles to research are the blood-brain barrier, which reduces the effectiveness of treatments, and the incomplete comprehension of the ethology of Alzheimer's disease. Stem cell-based therapy has been seen as a novel, reliable and successful restoration technique to treat AD since the condition is complex and has not gotten much attention. The latest advances in nanotechnology occasionally offer proactive treatment chances that can help get over limitations. In this overview, we concentrate on the causes of AD and the various methods used to treat them.

Exploring Neuroprotective Botanical Remedies in Neurodegenerative Conditions: A Review

Neuroprotection refers to the mechanisms and strategies used to protect the Central Nervous System (CNS) from neuronal injuries caused by neurodegenerative disorders. Neurodegenerative disorders are a type of chronic condition in which parts of the nervous system deteriorate over time, most notably the brain. These disorders have a slow and gradual effect on an individual. Neurodegeneration is a neuropathological condition and brain aging process. The brain pathology of neurodegenerative and cerebrovascular disease is a leading cause of death worldwide, with a death rate of approximately 8% and an incidence rate of approximately 2/1000. It is a major health issue in the twenty-first century. According to researchers, this disease affects over 50 million people worldwide. These disorders primarily affect people over the age of 65, and the World Health Organization predicts that this number will more than double in the next 30 years. Confusion, difficulty thinking, pain, muscle spasms, behavioral changes, paralysis, tremors, balance problems, coordination issues, hunched posture, and fatigue are symptoms of these disorders. These disorders are caused by age, genetics, medical history, habits, routine, and environment. This review article is focused on herbs such as Crocus sativus and Curcuma longa which are very helpful in Neurodegenerative diseases and serve as a resource for future research. Keywords: Neurodegeneration, Medicinal Herbs, Neuroprotection, Neuroprotective plants, Parkinson, Alzheimer.

Structural underpinnings and long-term effects of resilience in Parkinson’s disease

Resilience in neuroscience generally refers to an individual’s capacity to counteract the adverse effects of a neuropathological condition. While resilience mechanisms in Alzheimer’s disease are well-investigated, knowledge regarding its quantification, neurobiological underpinnings, network adaptations, and long-term effects in Parkinson’s disease is limited. Our study involved 151 Parkinson’s patients from the Parkinson’s Progression Marker Initiative Database with available Magnetic Resonance Imaging, Dopamine Transporter Single-Photon Emission Computed Tomography scans, and clinical information. We used an improved prediction model linking neuropathology to symptom severity to estimate individual resilience levels. Higher resilience levels were associated with a more active lifestyle, increased grey matter volume in motor-associated regions, a distinct structural connectivity network and maintenance of relative motor functioning for up to a decade. Overall, the results indicate that relative maintenance of motor function in Parkinson’s patients may be associated with greater neuronal substrate, allowing higher tolerance against neurodegenerative processes through dynamic network restructuring.

Evaluation of the Usability of a Serious Game in Virtual Reality with a Focus on the Perception and Experience of Health Professionals for Motor Rehabilitation in Children with Cerebral Palsy.

Introduction: Cerebral palsy (CP) is a nonprogressive neuropathological condition that requires lifelong neurocognitive-motor rehabilitation. Evidences indicate that the use of new technologies to assist in rehabilitation processes, such as serious games in virtual reality (VR), have served as adjuncts to therapy and capable of promoting engagement, motivation, and motor activation for these patients. Objective: To investigate the usability of a serious game in VR to help with the stability and balance of the head and trunk of children with CP, focusing on the perception and experience of health professionals. Methods: The collection was carried out with health professionals, and the results were comprehensively evaluated through viability by means of the total score, number of correct answers, number of errors, and level of difficulty during the execution of the game, which were collected from the performance report generated by the application. System satisfaction was also verified by the System Usability Scale (SUS). Results: The mean obtained from the total score of the SUS was 82.10 ± 12.66 points, being considered of high usability for the suggested purpose. The professionals' opinion about the usability of the system did not change due to the performance during the game. Conclusion: The study demonstrated that the developed rehabilitation program has successfully delivered the experience to exercise the head control and trunk balance of subjects with CP.

Discovery of triazole-bridged aryl adamantane analogs as an intriguing class of multifunctional agents for treatment of Alzheimer's disease

Alzheimer's disease (AD) is a progressive brain disorder associated with slow loss of brain functions leading to memory failure and modest changes in behavior. The multifactorial neuropathological condition is due to a depletion of cholinergic neurons and accumulation of amyloid-beta (Aβ) plaques. Recently, a multi-target-directed ligand (MTDL) strategy has emerged as a robust drug discovery tool to overcome current challenges. In this research work, we aimed to design and develop a library of triazole-bridged aryl adamantane analogs for the treatment of AD. All synthesized analogs were characterized and evaluated through various in vitro and in vivo biological studies. The optimal compounds 32 and 33 exhibited potent inhibitory activities against acetylcholinesterase (AChE) (32 - IC50 = 0.086 μM; 33 - 0.135 μM), and significant Aβ aggregation inhibition (20 μM). N-methyl-d-aspartate (NMDA) receptor (GluN1-1b/GluN2B subunit combination) antagonistic activity of compounds 32 and 33 measured upon heterologous expression in Xenopus laevis oocytes showed IC50 values of 3.00 μM and 2.86 μM, respectively. The compounds possessed good blood-brain barrier permeability in the PAMPA assay and were safe for SH-SY5Y neuroblastoma (10 μM) and HEK-293 cell lines (30 μM). Furthermore, in vivo behavioral studies in rats demonstrated that both compounds improved cognitive and spatial memory impairment at a dose of 10 mg/kg oral administration. Together, our findings suggest triazole-bridged aryl adamantane as a promising new scaffold for the development of anti-Alzheimer's drugs.

A model of neurovascular coupling and its application to cortical spreading depolarization

Cortical spreading depolarization (CSD) is a neuropathological condition involving propagating waves of neuronal silence, and is related to multiple diseases, such as migraine aura, traumatic brain injury (TBI), stroke, and cardiac arrest, as well as poor outcome of patients. While CSDs of different severity share similar roots on the ion exchange level, they can lead to different vascular responses (namely spreading hyperemia and spreading ischemia). In this paper, we propose a mathematical model relating neuronal activities to predict vascular changes as measured with near-infrared spectroscopy (NIRS) and fMRI recordings, and apply it to the extreme case of CSD, where sustained near-complete neuronal depolarization is seen. We utilize three serially connected models (namely, ion exchange, neurovascular coupling, and hemodynamic model) which are described by differential equations. Propagating waves of ion concentrations, as well as the associated vasodynamics and hemodynamics, are simulated by solving these equations. Our proposed model predicts vasodynamics and hemodynamics that agree both qualitatively and quantitatively with experimental literature. Mathematical modeling and simulation offer a powerful tool to help understand the underlying mechanisms of CSD and help interpret the data. In addition, it helps develop novel monitoring techniques prior to data collection. Our simulated results strongly suggest that fMRI is unable to reliably distinguish between spreading hyperemia and spreading ischemia, while NIRS signals are substantially distinct in the two cases.

How and why educational interventions work to increase knowledge of delirium among healthcare professionals in nursing homes: a protocol for a realist review

BackgroundDelirium is a neuropathological condition that impairs cognitive performance, attention and consciousness and can be potentially life-threatening. Nursing home residents are particularly vulnerable to developing delirium, but research thus far...

Uncovering tau in wasteosomes (corpora amylacea) of Alzheimer's disease patients.

Brain corpora amylacea, recently renamed as wasteosomes, are polyglucosan bodies that appear during aging and some neurodegenerative conditions. They collect waste substances and are part of a brain cleaning mechanism. For decades, studies on their composition have produced inconsistent results and the presence of tau protein in them has been controversial. In this work, we reanalyzed the presence of this protein in wasteosomes and we pointed out a methodological problem when immunolabeling. It is well known that to detect tau it is necessary to perform an antigen retrieval. However, in the case of wasteosomes, an excessive antigen retrieval with boiling dissolves their polyglucosan structure, releases the entrapped proteins and, thus, prevents their detection. After performing an adequate pre-treatment, with an intermediate time of boiling, we observed that some brain wasteosomes from patients with Alzheimer's disease (AD) contained tau, while we did not detect tau protein in those from non-AD patients. These observations pointed the different composition of wasteosomes depending on the neuropathological condition and reinforce the role of wasteosomes as waste containers.

Characterization of the agenesis of the corpus callosum, through the presentation of a clinical case

Agenesis of the corpus callosum (ACC) is an anomaly that consists of the partial or total absence, congenitally or due to a neuropathological condition, of this structure, due to alterations in development; thus being defined by its absence and not by its manifestations. The causes of agenesis of the corpus callosum have not yet been clear and it is proposed that it occurs due to multiple factors, such as vitamin deficiency, radiation exposure, prenatal and toxic infections, smoking, maternal diabetes and genetic causes. Prenatal diagnosis can be made by ultrasound and magnetic resonance imaging from week 20 of gestation. Neuroimaging diagnostic tools are useful and magnetic resonance imaging is one of the ideal and most sensitive methods for postnatal demonstration of the anomaly. The purpose of this research is to investigate the characteristics of agenesis of the corpus callosum, through the presentation of a clinical case where the relevant observations that allow its diagnosis are presented. The case presented highlights the importance of considering agenesis of the corpus callosum as a spectrum of clinical conditions that can present with a wide variety of signs and symptoms. In this report, a combination of neurological anomalies is observed, which highlight the complexity and diversity of this condition. Therefore, it is critical that healthcare professionals be alert to potential differential diagnoses and consider agenesis of the corpus callosum in the context of patients with neurological or developmental symptoms

Factors Associated to Progression of Hippocampal Sclerosis: Contribution of a New Staging System

AbstractBackgroundHippocampal sclerosis (HS) is a neuropathological condition with 5% to 30% of prevalence in the elderly (Nelson et al., 2013). HS is mostly associated with TDP‐43 proteinopathy, limbic‐predominant age‐related TDP‐43 encephalopathy (LATE) (Nelson et al., 2019), and usually coexists with other neurodegenerative disorders like Alzheimer´s (AD) and Lewy body disease (LBD). LATE is a progressive pathology that may combine with HS (LATE_HS+) in its advanced phases. We have developed a staging scheme for HS with a high correlation with TDP‐43 staging. Here we analyze the contribution of this classification system to understand the progression of HS in the context of focal TDP‐43 pathology in the medial temporal lobe (MTL).MethodA full postmortem neuropathological study was performed in 161 brains from a clinicopathological cohort of institutionalized dementia patients (Vallecas Alzheimer’s Center Study) (age at death = 87.4±6.6, sex ratio = 79% females) with a predominant primary diagnosis of AD (77.4%), followed by vascular dementia (11%) and LBD (7.3%), and a high prevalence of comorbid pathologies (TDP‐43 and various tauopathies). Four stages (1‐4) of HS, including early phases (pre‐HS), were applied based on histologic criteria. Demographic, clinical, and neuropathological variables showing correlation with HS stages were analyzed through factorial analysis.ResultSome stage of HS was present in 71.1% of patients, and 24% of them displayed an early HS stage. TDP‐43 inclusions were detected in 67.5% of the patients. Variables associated to HS stages were grouped in 4 factors. While age at death, survival time and MTL atrophy, grouped together (factor 1) explained 23% of total co‐variability, other factors included Braak tau and NIA‐B stages (20%) or alpha‐synuclein stages‐HS stages (4.5%). Interestingly, HS and TDP‐43 stages were also included in factor 1 and seggregated together into a further single factor (18%) as well.ConclusionOur staging scheme for hippocampal sclerosis identifies patients with LATE in early stages of HS, and suggests a complex interaction of factors involved in conversion of LATE_HS‐ to LATE_HS+. While TDP‐43 stages, age, survival time and atrophy stay closer to HS in the explanation of variability, Alzheimer’s tau and Lewy body pathologies appear as secondary co‐factors.

Cotard delusion, emotional experience and depersonalisation

ABSTRACT Introduction Cotard delusion—the delusional belief “I am dead”—is named after the French psychiatrist who first described it: Jules Cotard. Ramachandran and Blakeslee proposed that the idea “I am dead” comes to mind when a neuropathological condition has resulted in complete abolition of emotional responsivity to the world. The idea would arise as a putative explanation: if “I am dead” were true, there would be no emotional responsivity to the world. Methods We scrutinised the literature on people who expressed the delusional belief “I am dead”, looking for data on whether such patients are reported as entirely lacking in emotional responsivity. Results In numerous cases, patients with Cotard delusion are described as experiencing emotions including anxiety, fear, guilt, distress, euphoria and worry. Conclusions We conclude that complete absence of emotional responsivity cannot be what prompts the delusional idea that one is dead. We propose that, in at least some cases, the idea “I am dead” comes to mind in response to symptoms of depersonalisation or derealisation, often present in cases of Cotard delusion, and give examples of Cotard patients with abnormalities in various neural areas that could be responsible for the presence of such symptoms.

Computational attributes of protein kinase-C gamma C2-domain & virtual screening for small molecules: elucidation from meta-dynamics simulations & free-energy calculations

Epilepsy, a moderate to chronic neuropathological condition, is induced by the acute blockage of synaptic and voltage-gated inhibitory conduction or through the activation of synaptic and voltage-gated excitatory conduction. The regulation of long-term potentiation (LTP) is important in the regulation of epileptic events, and its activity is linked to specific protein kinases. The PKC-γ subtype is a vaguely explored therapeutic target for neurological disorders, but in selected studies, it is proven to be a critical intermediate protein in LTP. This study utilized computational modelling approaches including receptor-based docking, QSAR followed by explicit binding score assessment method MM/GBSA, MM/PBSA (EDA) and MTD simulation-based FES iteration. This was performed to virtually screen the small molecule libraries, which comprised about 2.79 lacs compounds against the Ca2+-binding site of the PKC-γ-C2 regulatory domain. The screened molecules LIG-41 ([4-Oxo-4-(4-phenylmethoxyanilino) butyl] azanium) and LIG-16 (Emixustat) exhibit overall optimal attributes in the above-mentioned parameters. The two leads are expected to inhibit the Ca2+-mediated PKC-γ activity. Communicated by Ramaswamy H. Sarma

Neurofilament Proteins as Biomarkers to Monitor Neurological Diseases and the Efficacy of Therapies.

Biomarkers of neurodegeneration and neuronal injury have the potential to improve diagnostic accuracy, disease monitoring, prognosis, and measure treatment efficacy. Neurofilament proteins (NfPs) are well suited as biomarkers in these contexts because they are major neuron-specific components that maintain structural integrity and are sensitive to neurodegeneration and neuronal injury across a wide range of neurologic diseases. Low levels of NfPs are constantly released from neurons into the extracellular space and ultimately reach the cerebrospinal fluid (CSF) and blood under physiological conditions throughout normal brain development, maturation, and aging. NfP levels in CSF and blood rise above normal in response to neuronal injury and neurodegeneration independently of cause. NfPs in CSF measured by lumbar puncture are about 40-fold more concentrated than in blood in healthy individuals. New ultra-sensitive methods now allow minimally invasive measurement of these low levels of NfPs in serum or plasma to track disease onset and progression in neurological disorders or nervous system injury and assess responses to therapeutic interventions. Any of the five Nf subunits – neurofilament light chain (NfL), neurofilament medium chain (NfM), neurofilament heavy chain (NfH), alpha-internexin (INA) and peripherin (PRPH) may be altered in a given neuropathological condition. In familial and sporadic Alzheimer’s disease (AD), plasma NfL levels may rise as early as 22 years before clinical onset in familial AD and 10 years before sporadic AD. The major determinants of elevated levels of NfPs and degradation fragments in CSF and blood are the magnitude of damaged or degenerating axons of fiber tracks, the affected axon caliber sizes and the rate of release of NfP and fragments at different stages of a given neurological disease or condition directly or indirectly affecting central nervous system (CNS) and/or peripheral nervous system (PNS). NfPs are rapidly emerging as transformative blood biomarkers in neurology providing novel insights into a wide range of neurological diseases and advancing clinical trials. Here we summarize the current understanding of intracellular NfP physiology, pathophysiology and extracellular kinetics of NfPs in biofluids and review the value and limitations of NfPs and degradation fragments as biomarkers of neurodegeneration and neuronal injury.

Effect of combining features generated through non-linear analysis and wavelet transform of EEG signals for the diagnosis of encephalopathy

Electroencephalogram (EEG) signals portray hidden neuronal interactions in the brain and indicate brain dynamics. These signals are dynamic, complex, chaotic and nonlinear, the nature of which is represented with features - fractal dimensions, entropies and chaotic features. This study aims at examining the discriminative power of individual features and their combination in the diagnosis of a neuro-pathological condition called encephalopathy. Feature combination is accomplished with the help of feature selection using Gini impurity score that improves discriminative power and keeps redundancy minimal. Further, three widely used non-parametric classifiers which are known to be effective with wavelet features on EEG signals — Support Vector Machine, Random Forest, Multilayer Perceptron — are employed for disease classification. The models created by the combination of aforementioned stages are analysed and evaluated with performance scores, leading to an optimal model for automated diagnostic applications.

Cell therapy and delivery strategies for spinal cord injury.

Spinal cord injury (SCI) is a complex neuropathological condition that represents a major challenge for clinicians and scientists due to patient's functional dysfunction and paralysis. Several treatments have been proposed including biological factors, drugs and cells administered in various ways. Stem cells arise as good candidates to treat SCI since they are known to secrete neurotrophic factors, improving neuroregeneration, but also due to their role in modulating the inflammatory process, favoring a pro-regenerative status. There are several types of cells that have been tested to treat SCI in experimental and clinical studies, but we still face many unanswered questions; one of them is the type of cells that can offer the best benefits and, also the ideal dose and administration routes. This review aimed to summarize recent research on cell treatment, focusing on current delivery strategies for SCI therapy and their effects in tissue repair and regeneration.

How glutamatergic synapse loss affects the firing rhythm of DG-CA3 model related with Alzheimer's disease.

As well known that synapse loss is a significant pathological feature of Alzheimer's disease (AD), meanwhile, the hippocampus is one of brain regions to be first affected in the early stage of AD. Thus, this work employs a comprehensive DG-CA3 network model of the hippocampus so as to explore the neuronal correlation between glutamatergic synapse loss and abnormal firing rhythm associated with AD from the perspective of neurocomputation. The neuropathological condition of glutamatergic synapse loss caused by the reduction of Shank3 protein in AD patients is imitated by decreasing glutamatergic excitatory synapse strength between different neurons. By means of power spectral analysis and dynamics technique, the numerical results reveal that excitability of pyramidal neuron as well as oriens lacunosum-moleculare (O-LM) cell in CA3 region is strongly degraded by the decrease of NMDA or AMPA-type glutamatergic excitatory synapse strength. Moreover, the relative power together with the peak of relative power density within alpha band is also diminished by decreasing glutamatergic synapse strength. These findings accord with the electrophysiological experiment of EEG that there is a decrease of alpha rhythm for AD patients, on the same time, they could highlight the significance of glutamatergic synapse loss in the pathogenesis of AD.

Curcumin Potentiates α7 Nicotinic Acetylcholine Receptors and Alleviates Autistic-Like Social Deficits and Brain Oxidative Stress Status in Mice.

Autistic spectrum disorder (ASD) refers to a group of neurodevelopmental disorders characterized by impaired social interaction and cognitive deficit, restricted repetitive behaviors, altered immune responses, and imbalanced oxidative stress status. In recent years, there has been a growing interest in studying the role of nicotinic acetylcholine receptors (nAChRs), specifically α7-nAChRs, in the CNS. Influence of agonists for α7-nAChRs on the cognitive behavior, learning, and memory formation has been demonstrated in neuro-pathological condition such as ASD and attention-deficit hyperactivity disorder (ADHD). Curcumin (CUR), the active compound of the spice turmeric, has been shown to act as a positive allosteric modulator of α7-nAChRs. Here we hypothesize that CUR, acting through α7-nAChRs, influences the neuropathology of ASD. In patch clamp studies, fast inward currents activated by choline, a selective agonist of α7-nAChRs, were significantly potentiated by CUR. Moreover, choline induced enhancement of spontaneous inhibitory postsynaptic currents was markedly increased in the presence of CUR. Furthermore, CUR (25, 50, and 100 mg/kg, i.p.) ameliorated dose-dependent social deficits without affecting locomotor activity or anxiety-like behaviors of tested male Black and Tan BRachyury (BTBR) mice. In addition, CUR (50 and 100 mg/kg, i.p.) mitigated oxidative stress status by restoring the decreased levels of superoxide dismutase (SOD) and catalase (CAT) in the hippocampus and the cerebellum of treated mice. Collectively, the observed results indicate that CUR potentiates α7-nAChRs in native central nervous system neurons, mitigates disturbed oxidative stress, and alleviates ASD-like features in BTBR mice used as an idiopathic rodent model of ASD, and may represent a promising novel pharmacological strategy for ASD treatment.

Alzheimer's disease and its treatment by different approaches: A review.

Alzheimer's disease (AD) is a neurodegenerative disorder that impairs mental ability development and interrupts neurocognitive function. This neuropathological condition is depicted by neurodegeneration, neural loss, and development of neurofibrillary tangles and Aβ plaques. There is also a greater risk of developing AD at a later age for people with cardiovascular diseases, hypertension and diabetes. In the biomedical sciences, effective treatment for Alzheimer's disease is a severe obstacle. There is no such treatment to cure Alzheimer's disease. The drug present in the market show only symptomatic relief. The cause of Alzheimer's disease is not fully understood and the blood-brain barrier restricts drug efficacy are two main factors that hamper research. Stem cell-based therapy has been seen as an effective, secure, and creative therapeutic solution to overcoming AD because of AD's multifactorial nature and inadequate care. Current developments in nanotechnology often offer possibilities for the delivery of active drug candidates to address certain limitations. The key nanoformulations being tested against AD include polymeric nanoparticles (NP), inorganic NPs and lipid-based NPs. Nano drug delivery systems are promising vehicles for targeting several therapeutic moieties by easing drug molecules' penetration across the CNS and improving their bioavailability. In this review, we focus on the causes of the AD and their treatment by different approaches.