Alzheimer’s disease and epilepsy: An increasingly recognized comorbidity

Yang, Fei; Chen, Liling; Yu, Yanying; Xu, Tingwan; Chen, Lu; Yang, Wenqian; Qian, Wei; Han, Yanbing

doi:10.3389/fnagi.2022.940515

Cited by 10 publications

(4 citation statements)

References 131 publications

(162 reference statements)

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“…A growing body of research has suggested an association between AD and epilepsy (18). Canine refractory epilepsy have a higher risk of developing CDS at a younger age than normal dogs (12).…”

Section: Discussionmentioning

confidence: 99%

“…Prior studies illustrated that Aβ can enhance neuronal excitability and contribute to seizures through a variety of mechanisms, including synaptic dysfunction and neuroinflammation (17,18). In addition, recent studies identified a potential link between Aβ and epilepsy-associated comorbidities, such as cognitive impairment and depression (18,25). These studies suggested a bidirectional relationship between seizures and Aβ accumulation in the brain.…”

Section: Introductionmentioning

confidence: 99%

“…Recent studies suggested that seizures can contribute to the formation of Aβ plaques in the brain and increase Aβ levels in cerebrospinal fluid (CSF), both of which are hallmarks of AD (21,23,24). Prior studies illustrated that Aβ can enhance neuronal excitability and contribute to seizures through a variety of mechanisms, including synaptic dysfunction and neuroinflammation (17,18). In addition, recent studies identified a potential link between Aβ and epilepsy-associated comorbidities, such as cognitive impairment and depression (18,25).…”

Section: Introductionmentioning

confidence: 99%

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Protein profiling and assessment of amyloid beta levels in plasma in canine refractory epilepsy

Phochantachinda,

Chantong,

Reamtong

et al. 2023

Front. Vet. Sci.

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IntroductionThe relationship between epilepsy and cognitive dysfunction has been investigated in canines, and memory impairment was prevalent in dogs with epilepsy. Additionally, canines with epilepsy have greater amyloid-β (Aβ) accumulation and neuronal degeneration than healthy controls. The present study investigated plasma Aβ42 levels and performed proteomic profiling in dogs with refractory epilepsy and healthy dogs.MethodsIn total, eight dogs, including four healthy dogs and four dogs with epilepsy, were included in the study. Blood samples were collected to analyze Aβ42 levels and perform proteomic profiling. Changes in the plasma proteomic profiles of dogs were determined by nano liquid chromatography tandem mass spectrometry.Results and discussionThe plasma Aβ42 level was significantly higher in dogs with epilepsy (99 pg/mL) than in healthy dogs (5.9 pg/mL). In total, 155 proteins were identified, and of these, the expression of 40 proteins was altered in epilepsy. Among these proteins, which are linked to neurodegenerative diseases, 10 (25%) were downregulated in dogs with epilepsy, whereas 12 (30%) were upregulated. The expression of the acute phase proteins haptoglobin and α2-macroglobulin significantly differed between the groups. Complement factor H and ceruloplasmin were only detected in epilepsy dogs, suggesting that neuroinflammation plays a role in epileptic seizures. Gelsolin, which is involved in cellular processes and cytoskeletal organization, was only detected in healthy dogs. Gene Ontology annotation revealed that epilepsy can potentially interfere with biological processes, including cellular processes, localization, and responses to stimuli. Seizures compromised key molecular functions, including catalytic activity, molecular function regulation, and binding. Defense/immunity proteins were most significantly modified during the development of epilepsy. In Kyoto Encyclopedia of Genes and Genomes pathway analysis, complement and coagulation cascades were the most relevant signaling pathways affected by seizures. The findings suggested that haptoglobin, ceruloplasmin, α2-macroglobulin, complement factor H, and gelsolin play roles in canine epilepsy and Aβ levels based on proteomic profiling. These proteins could represent diagnostic biomarkers that, after clinical validation, could be used in veterinary practice as well as proteins relevant to disease response pathways. To determine the precise mechanisms underlying these relationships and their implications in canine epilepsy, additional research is required.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Protein profiling and assessment of amyloid beta levels in plasma in canine refractory epilepsy

Phochantachinda,

Chantong,

Reamtong

et al. 2023

Front. Vet. Sci.

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“…Moreover, new evidence has linked Aβ-driven hyperactivity to subsequent aggregation and spreading of tau pathology 19 . Despite the evident comorbidity between neuronal hyperactivity and AD during the prodromic stage in patients, the origin of neuronal hyperexcitability and hippocampal vulnerability remain debated 20,21 . It is noteworthy that some reports have described hippocampal hyperactivity in asymptomatic offspring of autopsy-confirmed AD patients 22,23 .…”

Section: Introductionmentioning

confidence: 99%

Adenosine deficiency facilitates CA1 synaptic hyperexcitability in the presymptomatic phase of a knock in mouse model of Alzheimer’s disease

Bonzanni,

Braga,

Saito

et al. 2024

Preprint

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The disease's trajectory of Alzheimer's disease (AD) is associated with and worsened by hippocampal hyperexcitability. Here we show that during the asymptomatic stage in a knock in mouse model of Alzheimer's disease (APPNL-G-F/NL-G-F; APPKI), hippocampal hyperactivity occurs at the synaptic compartment, propagates to the soma and is manifesting at low frequencies of stimulation. We show that this aberrant excitability is associated with a deficient adenosine tone, an inhibitory neuromodulator, driven by reduced levels of CD39/73 enzymes, responsible for the extracellular ATP-to-adenosine conversion. Both pharmacologic (adenosine kinase inhibitor) and non-pharmacologic (ketogenic diet) restorations of the adenosine tone successfully normalize hippocampal neuronal activity. Our results demonstrated that neuronal hyperexcitability during the asymptomatic stage of a KI model of Alzheimer's disease originated at the synaptic compartment and is associated with adenosine deficient tone. These results extend our comprehension of the hippocampal vulnerability associated with the asymptomatic stage of Alzheimer's disease.

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Treatment Strategies for Alzheimer’s Disease-Associated Epilepsy: Past, Present, and Future Approaches

Liew

Arulsamy

Shaikh

2023

Handbook of Neurodegenerative Disorders

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Alzheimer’s disease and epilepsy: An increasingly recognized comorbidity

Cited by 10 publications

References 131 publications

Protein profiling and assessment of amyloid beta levels in plasma in canine refractory epilepsy

Protein profiling and assessment of amyloid beta levels in plasma in canine refractory epilepsy

Adenosine deficiency facilitates CA1 synaptic hyperexcitability in the presymptomatic phase of a knock in mouse model of Alzheimer’s disease

Treatment Strategies for Alzheimer’s Disease-Associated Epilepsy: Past, Present, and Future Approaches

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