Journal of Alzheimer's Disease最新文献

{"title":"Disruptive resting state networks characterizing depressive comorbidity in Alzheimer's disease and mild cognitive impairment.","authors":"Alessandro von Gal, Dario Papa, Marco D'Auria, Laura Piccardi","doi":"10.1177/13872877251337770","DOIUrl":"https://doi.org/10.1177/13872877251337770","url":null,"abstract":"<p><p>BackgroundDepressive comorbidity in neurodegeneration has been shown to predict conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD). However, its pathophysiology is not completely understood.ObjectiveHere, we characterize aberrant functional resting state networks (RSNs) characterizing depressive comorbidity in both AD and MCI.MethodsWe conducted a systematic literature review on Scopus, PubMed, and Web of Science to extract experiments that compared resting state scans of depressed and non-depressed MCI or AD patients. We employed Activation Likelihood Estimation (ALE) meta-analysis on eligible studies resulting from the search, to describe regions of significant co-activation across studies.ResultsThe systematic search resulted in 17 experiments, with 303 participants in total. The ALE yielded 10 clusters of significant co-activation distributed in the five major RSNs and across cortico-basal ganglia-thalamic circuits.ConclusionsDepressive comorbidity in neurodegeneration presents signature aberrant resting-state fluctuations. Understanding these within- and between-network alterations may be useful for future diagnostic and therapeutic applications.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251337770"},"PeriodicalIF":3.4,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144004744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"¹⁸F-FDG PET for the differential diagnosis of Alzheimer's disease and frontotemporal lobar degeneration: A multicenter prospective study in Japan.","authors":"Kengo Ito, Yukihiko Washimi, Takashi Kato, Keisuke Suzuki, Yasuomi Ouchi, Chigusa Watanabe, Yoshihide Sunada, Yumiko Kutoku, Kazunari Ishii, Kenji Ishii, Michio Kitayama, Etsuro Matsubara, Noriyuki Kimura, Harumasa Takano, Hiroaki Adachi, Kazuhiro Hara, Takeshi Kawarabayashi, Mikio Shoji, Norio Sugimoto","doi":"10.1177/13872877251338691","DOIUrl":"https://doi.org/10.1177/13872877251338691","url":null,"abstract":"<p><p>Background¹⁸F-fluoro-2-deoxy-2-D-glucose positron emission tomography (¹⁸F-FDG PET) is a biomarker of neuronal injury, according to the revised National Institute on Aging-Alzheimer's Association criteria.ObjectiveThis multicenter prospective cohort study aimed to evaluate the value of ¹⁸F-FDG PET for differential diagnosis of Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD) in comparison with phosphorylated tau protein (p-tau181) in cerebrospinal fluid (CSF).MethodsIn total, 138 patients (AD, 119; FTLD, 19) from 11 participating institutions underwent clinical and neuropsychological examinations, magnetic resonance imaging (MRI), CSF examination, and ¹⁸F-FDG PET at baseline. The cases were visually classified into predefined dementia patterns using ¹⁸F-FDG PET by three experts. A region-of-interest (ROI)-based automated analysis of ¹⁸F-FDG PET was also performed. The participants were followed up for 12 months, and the clinical diagnosis of dementia was re-evaluated.ResultsThe sensitivity, specificity, and accuracy of the visual reading of¹⁸ F-FDG PET for differentiating AD from FTLD were 94%, 78%, and 92%, respectively. In contrast, those of p-tau181 in CSF were 62%, 79%, and 65%, respectively. The sensitivity, the primary endpoint, was 32% higher for ¹⁸F-FDG PET than for p-tau181 in CSF. Additionally, the accuracy, the secondary endpoint, was 27% higher for ¹⁸F-FDG PET than for p-tau181 in CSF. In addition to the visual reading of ¹⁸F-FDG PET, the ROI-based automated analysis showed sensitivity, specificity, and accuracy of 81%, 79%, and 81%, respectively.ConclusionsThis study showed that the diagnostic performance of ¹⁸F-FDG PET in differential diagnosis of AD and FTLD was higher than that of p-tau181 in CSF.Trial registrationUMIN-CTR (UMIN 000016427, https://www.umin.ac.jp/ctr/) and Japan Registry of Clinical Trials (jRCTs041180098, https://jrct.mhlw.go.jp/).</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251338691"},"PeriodicalIF":3.4,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sleep disturbances and disorders in the memory clinic: Self-report, actigraphy, and polysomnography.","authors":"Aaron Lam, Dexiao Kong, Angela L D'Rozario, Catriona Ireland, Rebekah M Ahmed, Zoe Menczel Schrire, Loren Mowszowski, Johannes Michaelian, Ron R Grunstein, Sharon L Naismith","doi":"10.1177/13872877251338065","DOIUrl":"https://doi.org/10.1177/13872877251338065","url":null,"abstract":"<p><p>BackgroundSleep disturbances are common in dementia but rarely studied in memory clinics.ObjectiveIn a memory clinic setting we aimed to (1) identify rates of obstructive sleep apnea (OSA), abnormal sleep duration, circadian phase shift, insomnia, poor sleep quality, and REM sleep behavior disorder (RBD); (2) assess concordance between self-reported and actigraphy-derived measures; investigate associations between sleep disturbances; and (3) neuropsychological performance and (4) cognitive status.MethodsAdults over 50 at a memory clinic between 2009-2024 were included. OSA was assessed via polysomnography and prior history. Sleep duration and circadian phase were measured by self-report and actigraphy. Self-report questionnaires evaluated insomnia, sleep quality, and RBD. Global cognition, processing speed, memory, and executive function were assessed. Analysis of Covariance and multinomial logistic regression examined the impact of OSA, sleep duration, insomnia, and sleep quality on cognition and cognitive status.Results1234 participants (Mage 67.2, 46%M) were included. 75.3% had OSA, while 12.7% were previously diagnosed. Insomnia affected 12.0%, 54.3% had poor sleep quality, and 14.2% endorsed RBD symptoms. Self-reported short (30.5%) and long (10.2%) sleep exceeded actigraphy rates (8.5% and 5.1%) with poor concordance between measures. OSA was linked to impaired global cognition and memory (p < 0.05). Prolonged sleep predicted deficits in global cognition, processing speed, memory, and executive function and a higher risk of aMCI (all p < 0.05). Poor sleep quality was linked to better memory (p < 0.05).ConclusionsDespite discrepancies between self-reported and objective prevalence rates, sleep disturbances are highly prevalent in memory clinics and impact cognition, necessitating further examination.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251338065"},"PeriodicalIF":3.4,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Codonopsis pilosula</i> polysaccharides alleviate neuronal apoptosis induced by endoplasmic reticulum stress-activated PERK-ATF4-CHOP signaling in APP/PS1 mice.","authors":"Yuanqin Cai, Xi Wang, Yang Xiang, Zhenning Wang, Qinghua Long, Chuhua Zeng","doi":"10.1177/13872877251339484","DOIUrl":"https://doi.org/10.1177/13872877251339484","url":null,"abstract":"<p><p>Background<i>Codonopsis polysaccharides</i> (CPPs) shows neuroprotective potential in Alzheimer's disease (AD) and may reduce neuronal apoptosis by modulating endoplasmic reticulum stress (ERS).ObjectiveTo investigate the protective mechanisms of CPPs against neuronal apoptosis in APP/PS1 mice, focusing on the ERS response and the PERK-ATF4-CHOP signaling pathway.MethodsAPP/PS1 mice were orally administered CPPs at different doses. Their learning and memory abilities were evaluated using the Morris water maze (MWM). The integrity of hippocampal neurons and senile plaque deposition were assessed using histopathology, immunohistochemistry, and immunofluorescence. The expression of amyloid-β (Aβ) plaques secretase protein, ERS markers, and apoptosis-related proteins was assessed using western blot analyses. The affinity of the PERK-ATF4-CHOP pathway and CPPs was analyzed and assessed using molecular docking.ResultsMWM testing revealed that CPPs improved the learning and memory abilities of APP/PS1 mice. Histopathological examination confirmed that CPPs reduced hippocampal neuronal apoptosis. Immunohistochemistry and immunofluorescence analysis showed that CPPs decreased Aβ protein expression and ERS. Western blot analysis further confirmed that CPPs reduced the expression of proteins related to Aβ synthesis; downregulated the expression of glucose-regulated protein 78 (GRP78), PERK, ATF4, CHOP, and Bcl-2 associated X protein (Bax), while upregulating the expression of B-cell lymphoma 2 (Bcl-2).ConclusionsThis study demonstrates that CPPs exert neuroprotective effects by targeting the PERK-ATF4-CHOP signaling pathway and alleviating ERS, suggesting a novel approach and potential therapeutic agent for AD treatment.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251339484"},"PeriodicalIF":3.4,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The fall-dementia connection: Synergistic effects of falls with genetic and health risk factors.","authors":"Zhongxuan Wang, Qi Wang, Chunying Fu, Xiang Li, Luyi Zhang, Xiaoyu Zhang, Dongshan Zhu","doi":"10.1177/13872877251333799","DOIUrl":"https://doi.org/10.1177/13872877251333799","url":null,"abstract":"<p><p>BackgroundFew studies have examined the inverse relationship between dementia and falls, i.e., whether falls before dementia are a herald of dementia.ObjectiveWe aimed to explore the relationship between fall experiences and risk of dementia, assessing how factors like <i>APOE</i> ε4 allele, family history of dementia, comorbidities, traumatic brain injury (TBI), and frailty modify this association.MethodsWe used data from the UK Biobank. We used Cox proportional hazards models to estimate the HRs and 95% CIs for the association between falls and all-cause dementia, Alzheimer's disease (AD), vascular dementia (VaD), and non-Alzheimer/non-vascular dementia (NAVD). The synergistic effects of fall experiences and <i>APOE</i>, dementia family history, cardiovascular disease (CVD), diabetes, TBI, frailty on dementia were also investigated.ResultsTotally, 403,502 participants were included. 99,832 people experienced at least one fall, and 4143 dementia cases were observed. People who experienced falls had a higher risk of all-cause dementia, AD, VaD, and NAVD, with HRs (95% CIs) of 1.71(1.61, 1.83), 1.33 (1.20, 1.47), 2.00 (1.74, 2.29), and 2.03 (1.84, 2.24), respectively. The risk of dementia increased with the number of falls and with falls occurring later in life (after age 60). Fall experiences had a synergistic effect with dementia risk factors (<i>APOE</i> ε4 allele, family history of dementia and comorbidities), TBI, and frailty, collectively increasing the risk of dementia.ConclusionsFalls before dementia were linked to a higher risk of dementia. The risk escalated with more falls and falls after age 60. Combining falls with risk factors further amplified dementia risk.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251333799"},"PeriodicalIF":3.4,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144063813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How much can biomarkers explain sociodemographic inequalities in cognitive dysfunction and cognitive impairment? Results from a machine learning model in the Health and Retirement Study.","authors":"Eric T Klopack, Mateo P Farina, Bharat Thyagarajan, Jessica D Faul, Eileen M Crimmins","doi":"10.1177/13872877251338063","DOIUrl":"https://doi.org/10.1177/13872877251338063","url":null,"abstract":"<p><p>BackgroundBiomarkers may be pathways by which social adversity affects cognitive aging and Alzheimer's disease and related dementias (ADRD) risk.ObjectiveHow much variance in cognitive dysfunction and cognitive impairment onset do blood-based and physiological biomarkers provide above and beyond easily attainable sociodemographic variables, and how much can biomarkers explain differences in cognitive functioning and ADRD by sociodemographic variables?MethodsWe utilize machine learning to generate measures of predicted cognitive dysfunction and cognitive impairment incidence based on 91 biomarkers, identify the relative importance of each biomarker, and examine how much these biomarkers mediate sociodemographic differences.ResultsMarkers related to cellular aging, neurodegeneration, diet and nutrition, immune functioning, and lung function were identified as important. Biomarkers mediated 47.2-77.3% of the variance associated with age, 22.7-35.2% of racial/ethnic differences in cognitive dysfunction, and 12.5-17.6% of educational differences.ConclusionsBiomarkers provide the potential to understand pathways linking sociodemographic characteristics to cognitive functioning and health. Future research should consider additional biomarkers and evaluate the specific systems that put people at risk for cognitive impairment.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251338063"},"PeriodicalIF":3.4,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Angiogenesis promotion of the transplantation of human amniotic mesenchymal stem cells via the Ang-1/Tie-2 signaling pathways in Alzheimer's disease model.","authors":"Rui Wu, Jing Guo, Yang Liu, Sirou Huang, Pingping Wu, Weiping Liu","doi":"10.1177/13872877251338687","DOIUrl":"https://doi.org/10.1177/13872877251338687","url":null,"abstract":"<p><p>BackgroundAlzheimer's disease (AD) is a progressive degenerative disease of the central nervous system, leading to cognitive decline, mental symptoms, and behavioral disorders. The comorbidity of cerebrovascular disease in AD patients will accelerate the development of cognitive impairment and dementia. Since the dysfunction of the cerebral vasculature is closely related to neuropathology in AD patients, the protection of cerebral microvascular function and the improvement of cerebral microcirculation may bring a potential path for AD treatment. Human amniotic mesenchymal cells (hAMSCs) as a more advantageous cellular therapy for AD are proven to improve AD model mice's learning and memory abilities significantly, but fewer studies on angiogenesis and blood-brain barrier recovery have been found.ObjectiveThe study aimed to analyze the changes in angiogenesis-related factors of hAMSCs transplantation in the AD model and explore the underlying molecular mechanism.MethodshAMSCs were injected into APP/PS1 and wild type (WT) mice via tail vein, and the hAMSCs distribution in the cerebral tissue and angiogenesis in the hippocampal tissues were observed.ResultshAMSCs were found in the cortex and hippocampal areas of APP/PS1 and WT mice. hAMSCs transplantation significantly increased CD31 and Tie-2 expression in AD mice compared with the control group.ConclusionsThe study indicates that hAMSCs can cross the blood-brain barrier and enter the cerebral tissue of the mouse, transplantation of hAMSCs may promote angiogenesis in the AD model. The Ang-1/Tie-2 signaling pathway may be a therapeutically attractive target for the hAMSCs treatment of AD.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251338687"},"PeriodicalIF":3.4,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144015415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EPRCN exerts neuroprotective function by regulating gut microbiota and restoring gut immune homeostasis in Alzheimer's disease model mice.","authors":"Ming-Jie Li, Meng-Ning Lan, Yao-Xuan Du, Yue Liu, Hua-Yue Zhang, Min Guo, Shi-Wei Liu, Hai-Yang Xia, Zheng-Jun Wu, Hua-Jun Zheng","doi":"10.1177/13872877251339762","DOIUrl":"https://doi.org/10.1177/13872877251339762","url":null,"abstract":"<p><p>BackgroundNo effective drug treatment is currently available for Alzheimer's disease (AD), highlighting the urgent need to develop efficient therapeutic options. We have developed a formula based on medicine and food homology (MFH) consisting of egg yolk oil, perilla seed oil, raphani seed oil, cinnamon oil, and noni puree (EPRCN), and demonstrated that it can treat AD by alleviating neuroinflammation and oxidative stress. However, whether EPRCN can improve AD by regulating gut microbiota remains unknown.ObjectiveThe current study aimed to evaluate the effect of EPRCN on regulating gut microbiota and neuroprotection.Methods16S rRNA sequencing was used to assess the structure of gut microbiota. Hematoxylin-eosin (HE) staining, qRT-PCR, and ELISA were used to evaluate gut inflammation. Detected indexes associated with cholinergic dysfunction and neuronal damage to investigate the neuroprotective effects of EPRCN.Results16S rRNA gene analysis revealed that EPRCN remodeled the gut microbiota, inhibited gut metabolic disorders, and promoted CoA biosynthesis in scopolamine-induced mice. EPRCN can ameliorates gut inflammation by activating the cholinergic anti-inflammatory pathway. The results further indicated that EPRCN improved cholinergic dysfunction by inhibiting the activity of acetylcholinesterase and restoring cholinergic receptors. Additionally, EPRCN administration suppressed the neuronal loss and elevated brain derived neurotrophic factor expression in hippocampus. Correlation analysis found that alteration of several gut microbes was associated with indexes improved by EPRCN.ConclusionsThese findings suggest that EPRCN may serve as a promising dietary intervention for treating AD by regulating the microbiota-gut-brain axis and exerting neuroprotective function.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251339762"},"PeriodicalIF":3.4,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlations between agitation and other neuropsychiatric symptoms in each stage of Alzheimer's disease: A re-analysis of CATIE-AD.","authors":"Tomoyuki Nagata, Shinichiro Nakajima, Shinsuke Kito, Shunichiro Shinagawa","doi":"10.1177/13872877251340402","DOIUrl":"https://doi.org/10.1177/13872877251340402","url":null,"abstract":"<p><p>BackgroundAmong neuropsychiatric symptoms (NPSs) of Alzheimer's disease (AD), agitation has been shown to occur commonly in the course of AD, overlapping or comorbid with other NPSs.ObjectiveThe proportion of patients with agitation and the severity of agitation appear to differ depending on the neurocognitive stage of AD, and knowledge about the characteristic comorbid symptom pattern may help in elucidation of the underlying mechanism.MethodsAmong 421 clinic-based patients with AD, we re-analyzed the dataset of the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE-AD) to examine the correlations between the scores for agitation and those for other Neuropsychiatric Inventory subscales in each neurocognitive stage of AD (mild, moderate, and severe) classified according to scores in Mini-Mental State Examination.ResultsThe scores for agitation were positively and robustly correlated with the scores for irritability in all stages of AD, and with the scores for anxiety in the moderate and severe stages. The scores for agitation were also correlated with those for sleep disorders in severe AD stage or disinhibition in the moderate AD stage. Multiple regression analysis identified irritability influencing the agitation in moderate and severe stages, and sleep disorders influencing the agitation in the severe stage.ConclusionsAs comorbid NPSs with agitation, characteristic affective, impulsive, and circadian abnormalities may be relevant to generate diverse subsyndromes in AD. Irritability consistently causes agitated behaviors, including refusal to take one's own care, and diurnal rhythm disorder in the severe AD stage may also cause poor acceptance for self-care.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251340402"},"PeriodicalIF":3.4,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144019747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunocal^®, a cysteine-rich whey protein, rescues reelin and reduces amyloid plaque burden in a transgenic amyloid-β protein precursor (hAβPP_SweInd) mouse model of Alzheimer's disease.","authors":"Alexandra Sandberg, Srivalli Puttagunta, Nathan Duval, Holly Fleming, Lilia Koza, Kade Hieber, Jessica Holsopple, Michael Reyna, Daniel Paredes, Daniel A Linseman","doi":"10.1177/13872877251338323","DOIUrl":"https://doi.org/10.1177/13872877251338323","url":null,"abstract":"<p><p>BackgroundDeficits in Reelin expression play a significant role in the pathogenesis of various neurological disorders, including schizophrenia and Alzheimer's disease (AD). Notably, Reelin-expressing neurons of the entorhinal cortex layer II are among the first to be affected in AD.ObjectiveStrategies aimed at correcting deficits in Reelin might provide a novel therapeutic approach for AD.MethodsHere, we examined the effects of the whey protein supplement and glutathione (GSH) precursor, Immunocal^®, on Reelin expression both in vitro in hippocampal-entorhinal cortex slices from rat brain and in vivo in the hAβPP_SweInd (J20) mouse model of AD<i>.</i>ResultsIncubation of brain slices with Immunocal^® increased Reelin expression at the mRNA and protein levels. Oral treatment with Immunocal^®, given <i>ad libitum</i> in drinking water beginning at 3 months of age, corrected a deficit in cortical GSH levels observed in untreated mice and preserved Reelin expression in the hippocampal-entorhinal cortex sub-region of 5-month-old J20 mice. We also assessed the long-term effects of Immunocal^® by treating J20 mice from 3 months old to 12 months old. Long-term Immunocal^® treatment preserved brain GSH and rescued Reelin mRNA and protein expression, while significantly reducing amyloid plaque formation in the entorhinal cortex and hippocampus of AD mice.ConclusionsThese findings suggest that Immunocal^® promotes Reelin expression in vitro and sustains brain GSH and Reelin expression while diminishing amyloid plaque load in the entorhinal cortex and hippocampus of J20 mice. Thus, Immunocal^® offers a promising therapeutic approach to enhance Reelin expression and curtail amyloid deposition in AD.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251338323"},"PeriodicalIF":3.4,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144021059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}