A haptoglobin (HP) structural variant alters the effect of <i>APOE</i> alleles on Alzheimer's disease

Bai, Haimeng; Naj, Adam C.; Benchek, Penelope; Dumitrescu, Logan; Hohman, Timothy J.; Hamilton‐Nelson, Kara L.; Kallianpur, Asha R.; Griswold, Anthony J.; Vardarajan, Badri N.; Martin, Eden R.; Beecham, Gary W.; Below, Jennifer E.; Schellenberg, Gerard D.; Mayeux, Richard; Farrer, Lindsay A.; Pericak‐Vance, Margaret A.; Haines, Jonathan L.; Bush, William S.

doi:10.1002/alz.13050

Cited by 1 publication

(2 citation statements)

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“…Plasma HP, which is primarily produced by hepatocytes in the liver, is a particularly important hemoglobin-binding protein that removes hemoglobin from the circulation ( 45 ). Various additional functions of HP have been discovered, including serving as an acute phase 2-acid response glycoprotein, an antioxidant of apolipoprotein E (APOE), an anti-inflammatory protein, and an Aβ clearance facilitator ( 46 , 47 ). In the current study, HP was significantly upregulated in the epilepsy group compared to that in the healthy control group.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, a significant positive correlation between the serum HP level and the severity of cognitive impairment was observed in patients with AD ( 47 , 50 ). This association is believed to occur through the modification of the effects of APOE, another genetic factor implicated in AD progression ( 46 ). Although research on the relationship among HP, epilepsy, and Aβ is currently limited, the present findings suggest possible links among these factors.…”

Section: Discussionmentioning

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%